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.[1]References
- In vitro sensitivity of human endometrial cancer cell lines to paclitaxel or irinotecan (CPT-11) in combination with other aniticancer drugs. Hiramatsu, H.P., Kikuchi, Y., Seto, H., Nagata, I. Anticancer Drugs (2000) [Pubmed]
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