Relationship Between HER-2/neu Gene Status and Chemosensitivity of Human Endometrial Cancer Cell Lines

摘要

We have evaluated the growth inhibitory effects of various anticancer drugs on human endometrial cancer cell lines (Ishikawa, HEC-1A, HEC-50B, HEC-59, and HEC-108). When in vitro sensitivity was defined as an IC_(50) lower than 10% of the peak plasma concentration, all endometrial cancer cells were sensitive to paclitaxel (Tx). When the combined effects of Tx with another drug were determined by median-effect analysis, Tx followed by cisplatin resulted in synergistic effects on all cell lines. Tx followed by SN-38 (the active metabolite of irinotecan) and etoposide followed by Tx also had synergistic effects on four cell lines. Tx followed by piraru-bicin (THP) and THP followed by Tx showed synergistic effects on three cell lines. We then evaluated the relationship between HER-2/neu gene status and the chemosensitivity of six endometrial cancer cells (SPAC-l-L was added to the cells described above). HER-2/neu overexpression, determined by immunohistochemistry (HercepTest; Dako, Carpinteria, CA, US A), was seen only in SPAC-l-L cells, which were the most resistant cells to Tx and doxorubicin (ADR) of the six cells. Induction of HER-2/neu overexpression by dexamethasone was seen in Ishikawa and HEC-lA cells. Furthermore, induction of HER-2/neu overexpression by Tx was seen in HEC-59 cells. Chemosensitivity of these HER-2/new-overexpressing cells to Tx and ADR varied with the change of HER-2/neu gene status. However, there was no common relationship between HER-2/neu gene status and chemosensitivity in all cells. The IC_(50) values of herceptin (Trastuzumab Roche; Basel, Switzerland; humanized antiHER-2/neu monoclonal antibody) in these cells were not obtained at the micromolar level. To confirm the results, further studies to quantify HER-2/neu gene amplification are needed.