| Ovarian tumor is one of the three maglinant tumors of female genital organ, it' s survival rate is still at about 25-30%. Chemotherapy is the most important treatment except for operation. The convetional front-line chemotherapy stratergy for advanced epithelial ovarian carcinoma has become adjuvant administration of platinum ( cisplatin, carplatin) plus paclitaxel. But resistance to platinum and paclitaxel made people focus on more antituomor active agents. Topotecan as one of them has been ractified by American FDA to treat SCLC (small cell lung cancer) and ovarian cancer. Jin xi su is China-made topotecan, it is camptothecin derivatives that are felt to exert their cytotoxic effects by targeting topoisomerase-I, it is believed that topoisomerase-I ceavable complex and interactions between thiscomplex and the replication machinery may lead to cell death. So topotecan exerts antitumor activity during DNA synthesis and it is cycle-phase specific agent. The study was designed to evaluate the inducing effect of topotecan on apoptosis of ovarian cancer SKOV3 compared with cisplatin, and the expression of related gene p53 and bcl-2. Ovarian cell line SKOV3 is drug resistant cell line. We suvey inhibition of colony formation of SKOV3 cells by topotecan through MTT( microculture tetrazolium assy), the outcome show us a dose-depend inhibition effect of topotecan on SKOV3 cell colony formation, after 24hs it' s IC50 is 588ng/ml. The inhibition effect of topotecan is the base of clinical application, especially to those platinum-resistant patients, what' s more, with enough support high dose topotecan means strong effect, thus exploring the maxium tolerated dose and enhancing antitumor activity isalways what we are after. Apoptosis and necrosis are all detected by TEM, which confirm it can induce not only apoptosis but also cell necrosis. Cell necrosis is also one of the ways by which drugs exert antitumor effect, but necrosis is the cause of toxicity side effect. We detect time-depend death morphological change of SKOV3 cells after using topotecan through phase contrast microscope and provide proof that topotecan has antitumor activity. We process cells on cover slip by HE staining and detect cells through high power objective and count and come to apoptosis index (AI). AI of group with and without drugs are all higher than contrast group(p<0.01) at the same time ,and AI increase with time prolonging. 16 hours after Topotecan action, AI of it has no significant difference with cisplatin(p>0. 05), but when the time reachs 24 hours, topotecan reach higher AI than cisplatin(p<0.05), so we can include thattopotecan can at least gain the same antitumor activity on SKOV3 cells and after 24 hours it has stronger action than cisplatin. What' s more, topotecan has special antitumor mechanism and has no cross-resistance with paclitaxel and has synergetic action with cisplatin and paclitaxel in vitro, so many research has taken topotecan as the first-line chemotherapy agent.P53 and bcl-2 are all important adjust gene during antitumor drugs induced apoptosis, the former is positive correlation, the later inhibit apoptosis. After topotecan and cisplatin act on SKOV3 cells, we measure expression of these two proteins by immunohistochemistry and detect expression of p53 in drug action group are all high than contrast group, it has significant difference,expression of bcl-2 between TPT-group and contrast group hasn' t significant difference(p>0. 05), but for cisplatin group, expression of bcl-2 is lower than contrastgroup (p<0. 01).We can included according above metioned that p53 induced apoptosis is an important way of topotecan action which is like cisplatin, but we also observed that there are difference of p53 expression between topotecan and cisplatin(42. 8 + 2. 44 % VS 52.1 + 4. 79%), and topotecan hase the same effect with cisplatin, these suggest that topotecan has p53 independ apoptosis way or it can intiate cell death through other way other than apoptosis. Upon our date, topotecan faied in decre...
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