平阳霉素固体植入式缓释剂间质化疗口腔鳞癌的实验研究

目的:制备含平阳霉素(PYM)原料药的可吸收固体植入式缓释剂,导入荷瘤裸鼠瘤体,实施组织内间质化疗,评价其抗肿瘤效应。方法:20只人舌鳞癌荷瘤裸鼠,随机分为5组,进行不同处理:①PYM固体缓释剂间质化疗;②PYM静脉化疗;③PYM瘤内注射;④缓释剂辅料瘤内植入;⑤生理盐水静脉注射空白对照。分别以肿瘤体积、组织学、分子生物学检测(TUNEL)和流式细胞术评价各组的抑瘤率、肿瘤细胞生长状态、凋亡指数及凋亡率,用SAS6.2软件包对抑瘤率、肿瘤细胞凋亡指数及凋亡率进行F检验。结果:①各组抑瘤率分别为(93.12±8.26)%(间质化疗组)、(57.57±2.90)%(静脉化疗组)、(55.20±4.28)%(瘤内注射组)和(22.48±3.74)%(辅料植入组);各组肿瘤细胞凋亡指数:15.88±0.80(间质化疗组)、6.80±0.59(静脉化疗组)、7.13±0.19(瘤内注射组)、3.0±0.37(辅料植入组)和2.2±0.18(生理盐水静注空白对照组);各组肿瘤细胞的凋亡率为:间质化疗组(27.80±13.78)%、瘤内注射组(13.13±0.35)%、静脉化疗组(6.81±0.89)%、辅料植入组(2.72±1.55)%和生理盐水静脉注射空白对照组(1.05±1.19)%。间质化疗组抑瘤率、肿瘤细胞凋亡指数及凋亡率显著高于其他各组(P<0.05);②间质化疗组肿瘤细胞增殖力下降,核分裂像罕见,细胞大量死亡或凋亡。结论:PYM固体植入式缓释剂间质化疗的抗癌效应优于其他给药方式,在体表肿瘤特别是口腔癌治疗中的应用前景乐观。

Experimental study of interstitial chemotherapy with PYM delivered from a solid implantable biodegradable polymer against human tongue SCC in tumor-bearing nude mice

PURPOSE: This study was to evaluate the antitumor efficacy of implantable sustained Pingyangmycin(PYM) release system as a polymer based biocompatible implant administrated interstitially in tumors on tumor-bearing nude mice. METHODS: 20 tumor-bearing nude mice established with Tca8113 cell line were divided into five groups .Interstitial chemotherapy (polymer rod each containing 0.1mg PYM was inserted into tumors through puncture needle with internal piston)was performed in mice of Group A , intravenous injection of PYM was made in mice of Group B ,intratumoral injection of PYM was given in mice of Group C,polymer rod without PYM was inserted into tumors in Group D and normal saline was intravenously injected in mice of Group E as control. Same total dosage of PYM was given in Group A ,B and C. Inhibition rate(IR) based on tumor measurement ,apoptosis index (AI) of tumor cells based on TUNEL, apoptosis rate(AT)of tumor cells determined by flow cytometry and histopathological appearances were evaluated and analyzed in different groups. F test was used for statistical analysis by SAS 6.2 software package. RESULTS: The results showed that RI, AT and AI in experimental group (Group A) was significantly higher than that in other groups(P<0.05). Histopathologically, the proliferation of the tumor cells was relatively suppressed in Group A. CONCLUSIONS:Biodegradable PYM- polymer implant may be an optimistic form of drug delivery system in clinic and interstitial chemotherapy is especially suitable for tumors in oral-maxillofacial regions because of easy administration of the implant into the relatively superficial tumors in the regions.