In vitro sensitivity of human endometrial cancer cell lines to paclitaxel or irinotecan (CPT-11) in combination with other aniticancer drugs.
We have evaluated the growth inhibitory effects of paclitaxel alone or irinotecan (CPT-11) alone and their combined effects with other drugs on human endometrial cancer cell lines. IC50 doses of paclitaxel (Tx), SN-38 (active metabolite of CPT-11; 7-ethyl-10-hydroxycamptothecin) and cisplatin, including other drugs which have been used for treatment of patients with endometrial cancer, were examined using five human endometrial cancer cell lines (Ishikawa, HEC-1A, HEC-50B, HEC-59 and HEC-108). When in vitro sensitivity was defined IC50 lower than 10% of the peak plasma concentration (PPC), all endometrial cancer cell lines were sensitive to paclitaxel and three of five endometrial cancer cell lines were sensitive to SN-38, whereas cisplatin was not active against any endometrial cancer cell lines used in this study. Regarding the other drugs, aclarubicin (ACR) and actinomycin D (ACD) were active against four of five endometrial cancer cell lines, etoposide (VP-16) and pirarubicin (THP) against two, and 5-fluorouracil (5-FU) against only one, while ifosfamide (4-OHIFO) was not active against any endometrial cancer cell lines. When combined effects of paclitaxel or SN-38 with other one drug were determined by the median-effect analysis, paclitaxel followed by cisplatin resulted in synergistic effects to all endometrial cancer cell lines. Paclitaxel followed by SN-38 also had synergistic effects to four cell lines. Sequential but not simultaneous administration of taxol and THP-adriamycin showed synergistic effects to three cell lines. In combinations of SN-38 with other drugs, simultaneous administration of SN-38 and cisplatin resulted in synergistic effects to all cell lines. It is noteworthy that ACD followed by SN-38 showed synergistic effects to all cell lines, and simultaneous treatment of ACD and SN-38 or SN-38 followed by ACD also resulted in synergistic effects to three cell lines. THP-adriamycin followed by SN-38 had synergistic effects to four cell lines. The present quantitative data analysis for synergism provides a basis for a rational design of clinical protocols for combination chemotherapy in patients with endometrial cancer of the uterus.
Hiramatsu
H P
HP
Department of Obstetrics and Gynecology, Seto Hospital, Tokorozawa, Saitama, Japan. QWL04765@nifty.ne.jp
Kikuchi
Y
Y
Seto
H
H
Nagata
I
I
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin