Induction of apoptpsis in multi-drug resistant oral cancer cells using Taxol alkaroid derived from Taxaceae

口腔鳞状细胞癌是口腔恶性肿瘤的主要类型，通常采用手术、放疗、化疗相结合的方法进行治疗。虽然已知癌细胞对一种抗癌药物产生耐药性，对另一种抗癌药物产生耐药性，尤其是对放疗产生耐药性。临床上，口腔癌的治疗一直处于化疗和放疗的抵抗状态，常规治疗无法治愈，令人担忧。紫杉醇（Taxol）是近年来发展起来的新型抗癌药物，其抗肿瘤作用与细胞分裂促进微管蛋白的合成有关。因此，紫杉醇的抗癌作用机制与常用的抗癌药物不同，提示紫杉醇对常用化疗药物耐药的肿瘤有较好的抗癌作用。涎腺腺癌细胞系（SAC）正常成纤维细胞和内皮细胞在培养中的生长测定。在所测试的细胞系中，SAC在体外显示出对泰素和顺铂比SCC更敏感，而SCC对泰素和顺铂相对耐药。另一方面，SCC比SAC对阿霉素更敏感。A431#4细胞系来源于人外阴鳞状细胞癌细胞系A431'，对顺铂和阿霉素的耐药率为3.5倍。虽然A431#4对紫杉醇的敏感性是亲本细胞系的2.5倍。结果提示，紫杉醇是一种有效的化疗药物候选药物，对耐药的口腔鳞状细胞癌。

Usually, squamous cell carcinom, the majority of malignant tumor of oral region, are treated for the combination with operation therapy radiation therapy and chemotherapy, Although it has known that the carcinoma cells, developed resistant to an anti-cancer drug aquire tolerance to another anti-cancer drugs, still more to radiation therapy. Clinicaly, it is worried about the treatment of oral cancer in state of resistance to chemotherapy and radiation therapy, because of impossible of ordinary cure. Paclitaxel(Taxol) is new anti-cancer drug developed recently and show anti-tumor effect interfereing with cell division to promote the synthesis of tubulin protein. Consequently the mechanism of anti-cancer effect of Taxol are different from usual anti-cancer drugs, it is suggested that good anti-cancer effect can be acquire with Taxol for resistant cancers to usual chemotherapy agents.In this study, we investigated the sensitivity to Taxol, cisplatin and adriamycin of squamous cellm carcinoma cell lines(SCC) , salivary gland adenocarcinoma cell lines (SAC) normal fibroblast and endothelial cell by growth assay in culture. Of the cell line tested, SAC were shown to be generally more sensitive to Taxol and cisplatin than SCC in vitro and SCC were relatively resistant to Taxol and cisplatin. On the other hand, SCC were more sensitive to adriamycin in comparison to SAC. And fibroblast and endotherial cell were shown almost same sensitivity to these anti-cancer drugs compared with SCC and SAC.A431#4 cell line, derived from squamous cell carcinoma cell line A431' of human vulva was shown to be 3.5-fold resistant to cisplatin and adriamycin. Although A431#4 was shown 2.5-fold sensitive to Taxol compared with parent cell line. This result sugested that Taxol is a candidate for effective chemotherapy agent to resistant squamous cell carcinoma of oral cancer to usual anti-cancer drugs.