Qingjie Fuzheng Granules regulates cancer cell proliferation,apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

BackgroundSonic Hedgehog (SHh) signaling pathway plays a critical role in cell proliferation, apoptosis, and tumor angiogenesis in various types of malignancies including colorectal cancer (CRC). Qingjie Fuzheng Granules (QFG) is a traditional Chinese medicinal formula, which has been clinically used in various cancer treatments, including CRC. In this study, we explored the potential molecular mechanisms of QFG treatment effects on CRC via the SHh pathway.MethodsA CRC HCT-116 xenograft mouse model was utilized for all experiments. Mice were treated with intra-gastric administration of 1 g/kg of QFG or saline 6 days a week for 28 days (4 weeks). Body weight, length and shortest diameter of the tumor were measured every 3 days. At the end of the treatment, the tumor weight was measured. TUNEL staining assays were used to detect tumor apoptosis. Western blot and immunohistochemistry (IHC) assays were used to detect the expression of relative proteins.ResultsIn our results, QFG inhibited the increase of tumor volume and weight, and exhibited no impact on mouse body weight. Furthermore, QFG significantly decreased the expression of SHh, Smo and Gli proteins, indicating the action of SHh signaling. Consequently, the expression of pro-proliferative survivin, Ki-67, Cyclin-D1 and CDK4 were decreased and expression of anti-proliferative p21 was increased. The pro-apoptotic Bax/Bcl-2 ratio, cle-caspase-3 and TUNEL-positive cell percentage in tumor tissues were increased. Meanwhile, the pro-angiogenic VEGF-A and VEGFR-2 expression was down-regulated.ConclusionsQFG inhibited CRC cell proliferation and promoted CRC cell apoptosis and tumor angiogenesis in vivo through the suppression of SHh pathway, suggesting that QFG could be a potential therapeutic drug for CRC.     

The role and status of fuzheng in cancer prevention and treatment

Traditional Chinese medicine （TCM） treatment of cancer has a long history, and is an important part of cancer prevention and control in China. Fuzheng, also called reinforcing healthy qi and supplementing the root, is the most funda- mental principle of TCM in cancer prevention and control. In recent decades, this treatment has been thoroughly studied and widely applied, and played a crucial role in cancer prevention and treatment. With regard to the treatment of malignant tumors, Chinese medicine is mainly used in the following areas： improving symptoms, enhancing the quality of life, reducing postop- erative recurrence and metastasis, increasing efficacy and decreasing toxicity together with radiotherapy and chemotherapy treatments, and to some extent prolonging the survival of advanced tumors.     

参芪扶正注射液联合化疗治疗晚期乳腺癌30例临床观察

目的 观察参芪扶正注射液联合化疗治疗晚期乳腺癌的临床疗效。方法 将60例患者采用数字表法随机分为治疗组(30例)与对照组(30例)。两组均采用相同的CTF方案化疗,21天为1个周期,2个周期评价疗效;治疗组同时加用参芪扶正注射液治疗。观察近期疗效、中医证候变化、生活质量变化、不良反应及免疫功能变化等。结果 治疗组与对照组近期总缓解率分别为500%、43.3%(P＞0.05);临床证候改善率治疗组与对照组分别为700%、46.7%(P＜0.05);生活质量改善率治疗组与对照组分别为76.7%、50.0%(P＜0.05);不良反应治疗组发生低于对照组(P＜0.05);治疗组治疗后CD⁺₃、CD⁺₄及CD⁺₄/CD⁺₈上升(P＜0.05),CD⁺₈下降(P＜0.01);对照组治疗前后无明显变化。结论 参芪扶正注射液能减轻化疗造成的骨髓抑制,可通过调节细胞免疫功能增强疗效,改善临床症状,提高生活质量,延长生存期。     

参芪扶正注射液对RAU大鼠外周血T细胞亚群的影响

目的：建立复发性口疮（RAU）大鼠动物模型，探讨参芪扶正注射液对RAU的免疫调节作用。方法：大鼠脊柱两侧注射大鼠口腔黏膜抗原乳化液，建模后将溃疡大鼠随机分为3组：对照组建模正常饮食水。参芪扶正注射液组大鼠按8ml／（kg·d）剂量灌胃，左旋咪唑组大鼠0．02g／（kg·d）剂量灌胃，均20d。分别于建模前，成模后用药前、给药后大鼠眼眶采血行免疫组化染色，CD4^＋．CD8^＋细胞计数并进行统计学分析。结果：实验大鼠于最后一次抗原注射6d后开始出现口腔溃疡。RAU大鼠CD4^＋、CD4^＋／CD8^＋细胞量较建模前降低。实验大鼠给药后，参芪扶正注射液组、左旋咪唑组外周血CD4^＋、CD4^＋／CD8^＋均有回升，较对照组有显著性差异（P〈0．05），参芪扶正注射液组与左旋咪唑组相比。差异无统计学意义。结论：参芪扶正注射液对RAU大鼠有一定的免疫调节作用,与左旋咪唑无明显差异。     

扶正化瘀片治疗肝炎后肝硬化的研究

Objective: To investigate the efficacy and safety of the Fuzheng Huayu Tablet (扶正化瘀片, FZHYT), which is used to reinforce qi and resolve stasis in patients with posthepatitic cirrhosis (PHC). Methods: A multicenter, randomized, controlled clinical trial was conducted in 180 patients with PHC. The patients were randomly assigned using random numbers to a treatment group treated with FZHYT and a placebo group; the treatment course was 6 months for both groups. Overall response, adverse events (AEs), and the 2-year survival rate were assessed after treatment. Evaluations were made on changes in liver function, liver fibrosis, coagulation, hemodynamics, degrees of esophagogastric varices, ascites, quality of life (QOL), and scores of main symptoms. Results: The overall response was significantly higher in the treatment group than the placebo group (86.7% vs. 62.2%, P<0.01). Patients in both groups had signi?cant improvements in liver function [total bilirubin (TBIL), albumin (ALB)], liver fibrosis [hyaluronic acid (HA), type Ⅳ collagen (CⅣ)], coagulation [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)], hemodynamics portal venous flow (PVF), and splenic vein flow (SVF) after treatment. Between-group comparisons showed that compared with the placebo group patients in the treatment group achieved significantly greater improvements in TBIL, ALB, HA, C Ⅳ, PT, APTT, PVF, SVF, time to ascites resolution, 2-year survival, QOL, and symptom scores (P<0.05 or P<0.01). There were no significant AEs during the treatment. Conclusions: FZHYT is effective and safe for the treatment of hepatic cirrhosis as it is associated with improved liver function, liver ?brosis, coagulation, portal hypertension state, QOL, 2-year survival rate, and fewer AEs.     

扶正抗癌汤对荷瘤裸鼠非特异性细胞免疫系统的作用

目的探讨扶正抗癌汤对体内自然杀伤细胞(NKcell)与其表面FasLigand(FasL/CD95L)分子表达的影响。方法24只6周龄裸鼠,随机分为生理盐水组、扶正抗癌汤组(后简称“扶正汤”组)及阿霉素组。按悬液移植法建立BEL7402裸鼠人肝癌移植模型。观察其成瘤情况,利用流式细胞术考察各组鼠脾NK细胞表面标记抗原CD49b、CD49bFasL共表达情况,并分析盐水组中两指标同移植瘤体积的相关关系。结果各组全部成瘤,生理盐水组中表达CD49b及CD49b与FasL共表达的脾细胞分别与瘤体积呈负相关(P<0.01,P<0.05),且表达CD49b的脾细胞与瘤体积相关系数绝对值较大。扶正抗癌汤组表达CD49b的脾细胞、CD49b与FasL共表达的脾细胞水平明显高于对照组(P<0.01)与阿霉素组(P<0.05)。结论移植瘤的发展与NK细胞水平有关。“扶正汤”能升高体内NK细胞水平,增强NK细胞FasL表达,抑制肿瘤发展。     

益气法对SMMC-7721和Hepa1-6肝癌细胞体外抑瘤作用和细胞周期影响的实验研究

目的:观察中医益气法对SMMC-7721和Hepa1-6肝癌细胞的体外抗癌作用;从细胞周期揭示扶正抗癌的作用机制;为采用中西结合治疗肝癌提供理论与实验依据,为肝癌的防治开辟新的研究领域。方法:运用细胞培养技术,采用现代药理学方法,MTT法从细胞水平评价益气法对肝癌细胞增殖的抑制作用。并采用流式细胞术(FCM)检测细胞周期变化,从细胞周期角度观察中医扶正治法对肝癌细胞周期的影响。结果:体外研究提示益气法对肝癌细胞具有不同程度的抑制作用,且这种抑制作用在一定范围内呈浓度依赖性,与空白组比较在50mg/mL浓度以上有统计学意义(P<0.05),益气各浓度组对两种不同的肝癌细胞有不同程度的G2/M期阻滞作用。结论:益气法在体外对肝癌细胞有抑制作用,益气法有G2/M阻滞作用。     

抗毒扶正1、2号方提取液体外抗SRS病毒细胞活性作用

目的:探讨抗毒扶正1、2号方提取液对SRS病毒细胞增殖的抑制作用,为艾滋病临床治疗提供实验依据。方法:将抗毒扶正1、2号方提取液倍比稀释若干浓度,加入SRS细胞体系。以[3H]-TdR掺入法和RT-PCR法观测抗毒扶正1、2号方提取液对SRS细胞增殖的影响。结果:抗毒扶正1、2号方提取液组cpm值均较阴性对照组有所降低,SRSmRNA表达较阴性对照组有所降低。结论:抗毒扶正1、2号方提取液均有抑制SRS病毒细胞增殖的作用,且随药物浓度的升高,抑制作用也逐渐增强。提示抗毒扶正1、2号方对SRS病毒细胞具杀伤作用,对艾滋病临床治疗中药抗毒扶正方的筛选具实用价值。     

参芪扶正注射液辅助NP方案治疗老年晚期非小细胞肺癌近期疗效

目的：观察参芪扶正注射液辅助NP方案治疗老年晚期非小细胞肺癌（NSCLC）近期疗效和毒性反应。方法：治疗组35例，对照组34例，长春瑞滨（NVB）25mg／m^２静脉推注，第1、8天，顺铂（PDD）30mg，静脉滴注，第1—4天；治疗组化疗期间常规静滴参芪扶正注射液250ml每日1次，连用10日。结果：两组近期疗效差异无显著性（P＞0．05）；治疗组血液毒性反应和恶心、呕吐发生率明显低于对照组，差异有显著性（P＜0．05）。所有不良反应均能耐受。结论：参芪扶正注射液辅助NP方案治疗老年晚期NSCLC安全有效，参芪扶正注射液对老年晚期NSCLC化疗有一定减毒作用。     

Clinical Effects of Shenqi Fuzheng Injection in the Neoadjuvant Chemotherapy for Local Advanced Breast Cancer and the Effects on T-lymphocyte Subsets

Objective: To evaluate clinical effects of Shenqi Fuzheng Injection (参芪抉正注射液) in the neoadjuvant chemotherapy for local advanced breast cancer and the effects on T-lymphocyte subsets. Methods: During the period from 2000 to 2005, 126 patients with local advanced breast cancer were treated with the neoadjuvant chemotherapy. They were randomly divided into the following two groups: a control group of 61 cases treated by chemotherapy alone and a study group of 65 cases treated by chemotherapy plus Shenqi Fuzheng Injection. All the cases of both groups were given the CEF (CTX 500 mg/m2, d1, 8; EPI 40 mg/m2, d1, 8; and 5-Fu 500 mg/m2, d1,8) regimen. The clinical effects, the effects on T-lymphocyte subgroup and NK cells, and the toxic side effects were observed. Results: All the patients completed two cycles of the chemotherapy, and the efficacy and the toxic side effects were evaluated. For the primary tumor in the breast, the total effective rate was 69.2% (45/65) in the study group and 49.2% (30/61) in the control group with a statistically significant difference in the intergroup comparison (χ2=5.251, P=0.022, < 0.05). There was no progression of the disease in both the groups, and there were no grade IV toxic side effects in the two groups. The major toxic responses were myelosuppression and gastrointestinal reaction, which were milder in the study group than the control group, and with a shorter recovery course in the former than the latter. Besides, an obvious rise of the T-lymphocyte subgroup and NK cells was found in the study group after the neoadjuvant chemotherapy, with a very significant difference from the controls (P<0.01). Conclusions: Shenqi Fuzheng Injection can improve and regulate immune function of the patients with local advanced breast cancer given the neoadjuvant chemotherapy, and therefore it can enhance the curative effect and reduce the side effect as well.