Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by lipoxygenase inhibitors: possible role of product(s) of lipoxygenase pathway

Induction of epidermal ornithine decarboxylase (ODC) by a topicalapplication of 12-O-tetradecanoylphorbol-13-acetate (TPA), atumor promoter, was inhibited by treatment of mouse skin withphenidone (3–90 µ mol/mouse), nordihydroguaiareticadd (30 µmol/mouse) or 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline(BW 755C, 30 µ/mouse), which are well-known lipoxygenaseinhibitors. Phenidone and BW 755C are also to be cyclooxygenaseinhibitors. Inhibition of TPA-induced ODC by indomethacin (1.12µmol/mouse), a selective cyclooxygenase inhibitor, wascounteracted by prostaglandin E₂(PGE₂) (140 nmol/mouse). Thiscounteracting effect of PGE₂ was reversed by the treatment ofmice with nordihydroguaiaretic acid (30 µmol/mouse) orphenidone (30 umol/mouse). ODC activity which was suppressedby nordihydroguaiaretic add or phenidone at a dose of 180 umol/mousewas not further inhibited by indomethadn (1.12 µmol/mouse).In addition, the counteracting action of PGE₂ (140 nmol/mouse)was not observed in mice treated with nordihydroguaiaretic acidor phenidone at a dose of 180 umol/mouse. Thus, the suppressiveeffect of nordihydroguaiaretic add or phenidone on the ODC inductionby TPA would be due to the inhibition of lipoxygenase. The abovefindings strongly suggest that not only cyclooxygenase product(i.e., PGE₂) but also lipoxygenase produces(s) are involvedin the mechanism of ODC induction in mouse epidermis, and alack of either cyclooxygenase product or lipoxygenase product(s)causes a failure of ODC induction by TPA.     

Plasma Prostaglandin Levels in Patients with Gynecologic Malignancies and Its Fluctuations during Chemotherapeutically-Induced Gastrointestinal Toxicity

Peripheral plasma prostaglandins (PGs) were assayed in 10 casesof gynecologic malignancies. In addition, fluctuations of PGlevels during chemotherapeutically-induced gastrointestinaltoxicity as well as those caused by a bolus infusion of steroidhormone were investigated. As a result, the level of PGE₂ inmost cases of gynecologic malignancies was seen above or aroundthe upper limit of that in healthy women. During chemotherapy,the levels of PGF₂ and thromboxane B₂, (TxB₂) increased significantlycompared to baseline levels (P < 0.05). A bolus infusionof steroid hormone did not bring about any noticeable changein any of the levels of PGF₂, TxB₂, PGE₂. or 6K. It may be Inferredfrom these findings that PGs are synthesized in tumor tissueitself and released into plasma. Also, the finding that thelevels of peripheral plasma PGs increased during chemotherapysuggested that such an increase in PG release could be one ofthe factors causing gastrointestinal toxicity. Based on thefact that there were no changes in levels of peripheral plasmaPGs due to the administration of steroid hormone, however, wefailed to support the proposal that steroid hormone suppressesthe release of PG.     

Fatty acid-induced modifications of mouse mammary alveolar lesions in organ culture

A newly developed adult RIII mouse mammary gland organ culturesystem was used to examine the effects of fatty acids and aprostaglandin synthase inhibitor on the survival and/or growthof lactogenic hormone-independent mammary alveolar lesions (MAL).The number of MAL per gland that persisted in the absence oflactogenic hormones was increased in cultures treated with arachidonicacid (24.0±3.4), and was decreased after treatment withstearic add (4.0 ± 3.4) or indomethadn (5.0 ±0.6). Arachidonic add also induced higher incorporation of [³H]thymidineinto the cellular DNA of MAL containing glands. A comparisonof [³H]arachidonic add uptake into intact (MAL containing) glandsand parenchymafree fat pads revealed a selectively higher incorporationof the labeled fatty add in the intact glands. Arachdionk addexposure produced higher cumulative amounts (4.02 ng) of prostaglandinE₂ (PGE₂) which was significantly Inhibited (1.66 ng) by indomethacin(p<0.001). In contrast, exposure to stearic acid did notlower PGE₂ levels below that of controls. A concomitant increasein MAL number and PGE₂ production by arachidonic add and a decreasein both caused by indomethacin suggest that arachidonic addconversion to PGE₂ may have a facilitative role in the survivalof MAL.     

Comparison of tumour promoter-induced prostaglandin E2 release in human and rat keratinocytes

Prostaglandin E₂ (PGE₂ is associated with phorbol esterinducedskin irritation and -our promotion, but the mechanism of actionis not fully understood and the role of keratinocyte-derivedPGE₂ is unclear. PGE₂ was recently reported to modulate keratinocytedifferentiation and phorbol-12-myrlstate-13-acetate (PMA), themast extensively studied phorbol ester turnour promoter in mouseskin, was shown to stimulate PGE₂ release in human keratinocytes.Preliminary data on PGE₂ release induced by PMA, mezerein, anthralin,durn dodecyl sulphate and acetic acid in human keratinocytecultures is compared to their response in rat keratinocytes.Our data confirms a previously published report on stimulationof PGE release by PMA in human keratinocytes and also demonstratesa difference in the magdtude of the PMA- and mezerein-inducedresponse between human and rat keratinocyte cultum at non-cytotoxicconcentrations. Cytotoxicity was evaluated by the Neutral Reduptake assay and a concentration that reduced cell viabilityto 50% of control was selected as a maximum concentration forsubsequent measurement of PGE₂ release. In contrast, anthralin,sodium dodecyl sulphate and acetic acid induced a similar degreeof PGE₂ release in human and rat keratinocyte cultures, butrelease was spedfically associated with a cytotoxic response.Non-cytotoxic concentrations of these three chemicals did notstimulate release of PGE₂. This study illustrates that PGE₂dose-response curves may reflect different mechanisms of actionthat may be intimately associated with skin irritant and tumourpromoting activity. The data indicates a possible species differencein keratinocyte response to PMA and rnezerein. The importantvalue of keratinocyte cultures for mechanistic studies of tumourpromotion and skin imtation is highlighted and further researchIs warranted into the potential role of intracellular pathways,which modulate keratinocyte differentiation and proliferation,in these processes.     

Characteristics of bradykinin and TPA increases in the PGE2 levels of human urothelial cells

Prostaglandins play a potential key role in the pathogenesisof urinary bladder cancer. Bradykinin and TPA increases in prostaglandin(PG)E₂ levels were compared in primary cultures of human urothelialcells. Increased PGE₂ levels were dependent upon the dose ofTPA and were not apparent until 30–60 min after additionof TPA, with larger increases occurring between 60 and 120 min.Stimulation was inhibited by cycloheximide. Addition of arachidonicacid to TPAstimulated cells increased PGE₂ to a level similarto that seen in arachidonic acid-stimulated controls, and thislevel was not altered by cycloheximide. In contrast to TPA,the bradykininincreased PGE₂ levels were maximal at 5 min (theearliest time-point assessed) and were not inhibited by cycloheximide.Increases in PGE₂ levels by both TPA and bradykinin requiredcalcium. Excessive stimulation by TPA resulted in a desensitizationto subsequent stimulation by TPA, but not bradykinin. Combinationof TPA with bradykinin produced at least an additive effecton PGE₂ levels. Both agonists increased the release of [³H]arachidonicacid over a timecourse similar to their PGE₂ response. Bradykininand TPA appear to increase PGE₂ levels by enhancing arachidonicacid availability through separate phospholipase pathways. Thus,human urothelial cells exhibit similar, but yet distinct profilesfor prostaglandin stimulation by TPA and bradykinin.     

12-O-Tetradecanoylphorbol-13-acetate and the induction of prostaglandin E2 generation by human keratinocytes: a re-evaluation

12-O-Tetradecanoylphorbol-13-acetate (TPA) induces prostaglandinE₂ (PGE₂ synthesis in mouse keratinocytes and is associatedwith the induction of keratinocyte proliferation as well asaccelerated differentiation. In human keratinocytes, TPA hasbeen reported not to induce the release of either ³H-labeledarachidonic acid or ³H-labeled prostaglandins, even though celldifferentiation is stimulated. Because PGE₂ has been associatedwith the modulation of cell differentiation and because of technicalproblems inherent in evaluating arachidonic acid metabolismusing only radlolabeled substrates, we evaluated the abilityof TPA to induce endogenous PGE₂ generation by cultured humankeratinocytes using a specific and sensitive enzyme immunoassay.With this technique, TPA was found to induce a dose-dependent(1.6x10^–12–1.6x10^–8 M) increase in PGE₂ generation.These results are consistent with observations made not onlyin mouse keratinocytes but in other mammalian and human celltypes. Documenting the ability of TPA to stimulate PGE₂ productionin human keratinocytes is very relevant to current theoriesregarding the role of PGE₂ In keratinocyte differentiation aswell as to establishing parallels between the murine and humanskin models.     

7, 8-Benzoflavone: an inhibitor of prostaglandin synthesis and ornithine decarboxylase in murine epidermal cultures

7, 8-Benzoflavone (7, 8-BF), over a dose range of 0.1 -10 µM,partially inhibited the synthesis of prostaglandin E₂ (PGE₂)in primary cultures of epidermal cells fron SENCAR mice, andcompletely suppressed the TPA-dependent stimulation of PGE₂synthesis. Under identical conditions 7, 8-BF also partiallysuppressed ornithine decarboxylase (ODC) activity in both unstimulatedand TPA stimulated cultures.The finding that 7, 8-BF inhibitionof TPA-induced ODC can not be overcome by addition of exogenousPGE₂ suggests that ODC induction by TPA involves a prostaglandin-independentcomponent.     

Modulating effect of amount and types of dietary fat on ornithine decarboxylase, tyrosine protein kinase and prostaglandins production during colon carcinogenesis in male F344 rats

Epidemiologcal and laboratory animal model studies suggest thatthe effect of dietary fat on colon carcinogenesis depends onthe amount and its type. In the present study, we investigatedthe modulating effect of high-fat diets rich in omega-3, omega-6and omega-9 fatty adds on liver, colon and small intestine mucosalornithine decarboxylase (ODC) and tyrosine-specific proteinkinase (TPK) activities and plasma, liver and colon mucosalprostaglandin E₂ (PGE₂) and 6-keto prostaglandin F₁     

Prostaglandins, cyclic nucleotides and the effect of phorbol ester tumor promoters on mouse skin in vivo

Topical application of prostaglandin E₁ or E₂ onto the mouseskin results in a 2- to 3-fold increase of the cyclic AMP levelin epidermis within 5 min. (15S)-15-methyl-PGE₁ is more activein this respect, whereas PGD₂ and PGF₂ are ineffective. Thelevel of cyclic GMP is not altered by E- or F-prostaglandins.A single PGE₂ application desensitizes the cyclic AMP responseof mouse epidermis to further treatments in a dose dependentand agonist-specific manner. Delayed and long-lasting refractorinessof PGE₂-induced cyclic AMP accumulation is also caused by hyperplasiogenicskin irritants such as the phorbol ester tumor promoter TPAor the non-promoting agents RPA and A23187 [GenBank] . The non-irritantskin mitogen 4-O-methyl-TPA does not evoke desensitization.TPA-induced PGE2 refractoriness cannot be prevented by inhibitorsof protein synthesis, anti-inflammatory steroids, in-domethacinor phentolamine. The development of tachyphyl-axis does notseem to be related to endogenous formation of PGE or cyclicAMP. A 2-fold increase of epidermal cyclic AMP observed within1–2 h of TPA application can be inhibited by indomethacintreatment and correlates with delayed accumulation of PGE₂ inTPA-treated epidermis, whilst immediate PGE accumulation (5–10min after TPA application) which has been shown to be criticalfor development of TPA-induced epidermal hyperplasia is notaccompanied by any change of the intraepidermal cyclic AMP level.It is concluded that mouse epidermis contains two types of PGE-regulatedeffector systems, one of which is coupled to adenylate cyclase,one of which is not. Only the latter system is involved in theinduction of hyperplasia. At least as far as the mitogenic effectis concerned, cyclic AMP does not seem to be involved in TPAaction.     

葡萄糖和胰岛素对Colon26肿瘤细胞分泌TGF-β1的影响

 目的 探讨葡萄糖和胰岛素浓度的变化对Colon26肿瘤细胞分泌TGF-β₁的影响。 方法 体外常规培养Colon26肿瘤细胞,根据所用培养液外加葡萄糖和胰岛素浓度的不同,将实验所用细胞分为12组,培养48小时后收集上清液,ELISA法检测TGF-β₁的浓度。 结果 (1)D组上清液TGF-β1的浓度明显高于A组,差异有统计学意义(P<0.01);而B、C组上清液TGF-β1的浓度与A组相比差异均无统计学意义(P>0.05)。（2）E、F、G组上清液TGF-β₁的浓度与A组相比,对Colon26肿瘤细胞上清液TGF-β₁的分泌差异无统计学意义(P>0.05)。（3）L、M、N组上清液TGF-β₁的浓度均明显高于A组,差异有统计学意义(P<0.01); 而H、K组上清液TGF-β₁的浓度与A组相比差异无统计学意义(P>0.05)。 结论 （1）高浓度的葡萄糖能够增加Colon26肿瘤细胞培养上清TGF-β₁的分泌。（2）不同浓度的胰岛素不影响Colon26肿瘤细胞TGF-β₁的分泌。     

VEGF165在HepG2体外形成血管生成拟态中的作用

 目的 探讨VEGF₁₆₅在人肝癌细胞株HepG2体外形成血管生成拟态（Vasculogenic mimicry,VM）中的作用。方法 三维细胞培养HepG2,观察其形成血管样通道的能力;构建pcDNA3.0 VEGF165和pcDNA3.0-VEGF₁₆₅b 真核表达质粒,以Lipofectamine2000转染HepG2细胞,RT-PCR及Western blot检测转染后各组细胞VEGF165和VEGF₁₆₅b的表达;三维培养转染后HepG2细胞,观察各组细胞形成血管生成拟态的能力。结果 HepG2细胞在三维细胞培养系统中可形成血管样通道;VEGF₁₆₅及VEGF₁₆₅b真核表达质粒转染HepG2细胞后,RT-PCR及Western blot均示VEGF165和VEGF₁₆₅b表达分别上调,而转染VEGF₁₆₅b质粒组VEGF₁₆₅表达下调;三维细胞培养转染后的HepG2细胞,各组形成血管生成拟态的能力无明显区别。结论 HepG2细胞可于三维培养系统中形成管道结构,但VEGF165对HepG2细胞体外形成血管生成拟态的能力无明显影响。     

Regulation of dog urothelial cell arachidonic acid release and prostaglandin E2 synthesis

The effects of various agonists on prostaglandin E₂ (PGE₂) synthesisand arachidonic acid release were evaluated to identify factorswhich regulate urothelial cell responsiveness. Techniques forharvesting and culturing urothelial cells from the canine bladderwere developed. Although serum had little effect on growth,it was required for arachidonic acid, 12-O-tetradecanoylphorbol-13-acetate(TPA) or A23187 to elicit increases in PGE2 production. Fetalcalf serum (FCS), bovine can serum (BCS) and heated BCS (eachat 1%) were equally effective in supporting prostaglandin production.The optimum concentration range for the effect of FCS was 0.3–1.0%with 7.0% being less effective. The lack of agonist responsivenessobserved with no serum could be reversed by adding serum atdays 2 or 6 of a total of 9 days in culture. Subculturing cellsdramatically reduced responsiveness to all stimulators tested.Bradykinin-stimulated release of arachidonic acid was maximalwithin 15 min, while the TPA release continued throughout the120-min study. TPA response was inhibited by cycloheximide andactinomycin D. Neither agent altered the response to arachidonicacid. Combinations of arachidonic acid with TPA were neitheradditive nor synergistic. Responses to arachidonic acid, TPAand A23187 were optimum when the cells were near confluency.NaF, epidermal growth factor and mezerein also stimulated PGE₂synthesis. Tumor-promoting, but not the non-tumor-promotingphorbol esters (4-phorbol-12,13-didecanoate), increased PGE₂synthesis. Thus, the arachidonic acid cascade in dog urothelialcells is a hormonal responsive system which provides a methodfor evaluating transmembrane signaling.     

COX-2 选择性抑制剂Celecoxib 治疗胶质瘤的体内实验研究

 目的 探讨选择性环氧化酶-2抑制剂Celecoxib(塞来昔布)对C6胶质瘤生长抑制的体内实验研究。方法 将成瘤小鼠分为对照组和治疗组，应用肿瘤HE染色法、肿瘤生长曲线、前列腺素E2(PGB)检测及电镜检查方法观察Celecoxib对小鼠移植瘤的作用。结果 HE染色和电镜可见治疗组血管破坏、细胞坏死和凋亡，PGE2检测及肿瘤生长曲线分析有统计学意义，P<0．05。结论 Celecoxib能够抑制COX-2活性。降低PGB合成，Celecoxib对C6胶质瘤生长具有抑制作用，对胶质瘤的治疗有重要意义。     

Smad4和Smad7在人脑胶质瘤中的表达及意义

 目的 探讨Smad₄和Smad₇在人脑胶质瘤中的表达及意义。方法 采用免疫组化方法,对临床经过石蜡包埋的30例胶质瘤和8例正常脑组织标本进行定位和定性检测。结果 Smad₄和Smad₇蛋白在胶质瘤中有不同程度的表达,在正常脑组织、低、高级别胶质瘤中Smad₄的阳性表达分别为44．80±16．19,25．81±9．48,6．73±3．71,P<0．05。Smad₇的阳性表达分别为6．69±3．86,18．22±7．84,41．95±17．27,P<0．05。差别均有显著意义。且Smad4与Smad7的表达水平呈负相关,r=-0．82,P<0．01。结论 Smad₄随胶质瘤的病理分级增高阳性表达降低,对胶质瘤的进展有抑制作用。Smad₇则相反,可能参与了胶质瘤的恶性进展。     

Responses of rat urine and urothelium to bladder tumor promoters: possible roles of prostaglandin E2 and ascorbic acid synthesis in bladder carcinogenesis

An investigation of sequential changes in urine composition,levels of DNA synthesis and morphology of bladder epitheliumfollowing administration of the tumor promoters sodium ascorbate(AsA-Na) or butylated hydroxyanisole (BHA) and the non-promoterascorbic acid (AsA) for 36 weeks was performed. In addition,prostaglandin E₂ (PGE₂), cAMP and AsA content were assessedin bladder tissue after 16 weeks. While AsA-Na caused increasein pH, sodium content and volume, and a decrease in osmolalityof the urine throughout the study, these changes were not observedwith AsA administration which resulted in a decrease in urinarypH. BHA treatment was not associated with any urinary changes.AsA-Na brought about a significant elevation of DNA synthesisin the bladder epithelium from weeks 2 to 16 and was associatedwith simple hyperplasia at week 8, which, however, decreasedby week 16 and was no longer evident at weeks 24 and 36 whenDNA synthesis returned to normal. Under the scanning electronmicroscope (SEM), morphologic alterations of the urothelialsurface in rats given AsA-Na were observed at weeks 8 and 16,but the appearance at week 36 was almost normal. AsA did notcause any changes in these parameters at any time point. BHAinduced a significant elevation of DNA synthesis throughoutthe study, produced simple hyperplasia at week 36 and alterationsof the epithelial surface from weeks 4 to 36. Significant increasesof PGE₂ and AsA in bladder tissue were noted for the AsA-Naor BHA, but not AsA groups. Moreover, cAMP levels in bladdertissue of rats exposed to AsA-Na or BHA were slightly higherthan in the controls. The results suggest that changes in PGE₂,cAMP and AsA may be involved in promotion of rat bladder carcinogenesis.     

Prostaglandin modulation of phorbol ester skin tumor promotion

TPA promotion of skin tumors in mice can be modified by applicationof various prostaglandins or their precursors. The effects dependon the particular prostaglandin used: PGF₂ enhances promotion,whereas PGE₁ consistently inhibits promotion. Time of applicationof the prostaglandin with respect to TPA determines whetherPGE₂ enhances or inhibits. Dose-dependent inhibition was observedfor arachidonic acid. The prostaglandins alone were unable toelicit tumors in initiated mice.     

Possible therapeutic role of vitamin D3 in aggressive fibromatosis

Desmoids, also known as aggressive fibromatoses, are locallyinvasive tumors that are intermediate in their biological behaviorthat lies between benign fibrous proliferations and low-gradefibrosarcomas. In this report, we present a case of a youngfemale patient with a huge tumoral mass located in the rightshoulder region that recurred after total resection and wasresistant to radio-chemo-hormonal therapy. Eventually, she respondedto 1,25-(OH)₂-vitamin D₃ treatment.     

Eicosanoids and multistage carcinogenesis in NMRI mouse skin: role of prostaglandins E and F in conversion (first stage of tumor promotion) and promotion (second stage of tumor promotion)

When applied to NMRI mouse skin in vivo, phorbol esters suchas 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate(RPA) have been found to induce two early waves of prostaglandinE₂ (PGE₂) synthesis after 15 and 90 min and a delayed accumulationof prostaglandin F₂ (PGF₂) after 2 h. With respect to PGF₂ formationdifferent activities of both agents were observed, in that TPAbut not RPA induced additional PGF waves after 4 and 17 h. Functionally,PGE₂ was previously shown to be an endogenous mediator of theTPA- or RPA-induced epidermal hyperproliferation and hyperplasia.A functional role of PGF could be attributed to the post-initiationstages of tumor development in initiated mouse skin, i.e. theconversion stage (stage I of tumor promotion) elicited by twoTPA applications and the promotion stage (stage II of promotion)brought about repetitive RPA treatments. PGF₂, appearing asone distinct biosynthetic wave 3–4 h after TPA applicationseems to be critically involved in the conversion steps since(i) inhibition of its accumulation by indomethacin led to aninhibition of tumor formation, (ii) the inhibitory effect ofindomethacin could be reversed by PGF₂ and (iii) RPA was notable to give rise to the accumulation of PGF₂ 4 h after applicationas obtained by TPA treatment. Moreover, RPA-induced promotionof DMBA- and TPA-treated mouse skin was inhibited by indomethacin.The inhibitory effect of indomethacin on papilloma formationwas again reversed by PGF treatment concomitant with RPA.     

蒿甲醚对SD大鼠原位脑胶质瘤的抑瘤实验

目的探讨蒿甲醚（Artemether）对SD大鼠原位脑胶质瘤的抑瘤作用。方法采用四甲基偶氮唑蓝(MTT)法测定不同浓度蒿甲醚对大鼠C₆脑胶质瘤细胞株的生长抑制作用,计算半数抑制浓度(IC₅₀)。立体定位仪对48只（雌、雄各半）SD大鼠建立脑胶质瘤原位模型,随机分为6组：对照组;模型组,蒿甲醚33.3 mg/（kg·d）、50.0 mg/（kg·d）、66.6 mg/（kg·d）;联合用药组,蒿甲醚50.0 mg/（kg·d）+ 硫酸亚铁1.5 mg/（kg·d）;阳性药对照组。采用灌胃给药法连续给予各组SD大鼠用药10天,对照组给予0.9%氯化钠溶液。肿瘤体积按a²bπ∕6(a为肿瘤的短径,b为肿瘤的长径)计算。全脑标本用4%多聚甲醛固定。肿瘤组织做病理观察。结果蒿甲醚抑制大鼠C₆脑胶质瘤细胞增殖,其抑制作用呈剂量和时间依赖性;模型组和联合用药组对SD大鼠原位脑胶质瘤的抑瘤率分别为：54.5%、61.0%、64.5%和69.8%;模型组组间比较,蒿甲醚66.6 mg/（kg·d）用药组的抑瘤率明显高于蒿甲醚33.3 mg/（kg·d）用药组;各实验组间比较,联合用药组的抑瘤率显著高于模型组33.3 mg/（kg·d）。结论口服蒿甲醚对SD大鼠脑部原位接种C₆脑胶质瘤有明显的抑瘤作用。     

体外模拟CO2气腹环境对宫颈癌细胞生长与转移的影响

 目的 研究体外模拟CO₂气腹环境对宫颈癌细胞生长与浸润转移的影响。方法 利用宫颈癌细胞作为研究对象,建立体外CO₂气腹模型,将宫颈癌细胞经不同压强、不同时间CO₂作用后, 测定细胞生长曲线、细胞集落形成、细胞生长周期、细胞侵袭黏附迁移能力。观察癌细胞生长浸润转移的变化。结果 经CO₂作用后,宫颈癌细胞的生长增殖在受到短暂抑制后,增殖能力明显增强,但与CO₂压力的改变无关;宫颈癌细胞的侵袭、迁移和黏附能力显著下降。结论 CO₂对宫颈癌细胞的生长增殖能力起先抑制后促进的作用;对宫颈癌细胞的浸润转移能力是抑制的。