Higher sensitivity to patupilone versus paclitaxel chemotherapy in primary uterine serous papillary carcinoma cell lines with high versus low HER-2eu expression in vitro.

摘要

OBJECTIVE: To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine serous papillary carcinoma (USPC) with high versus low HER-2eu expression. METHODS: Six primary USPC cell lines, half of which overexpress HER-2eu at a 3+ level, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. Quantitative RT-PCR was used to identify potential mechanisms underlying the differential sensitivity/resistance to patupilone versus paclitaxel in primary USPC cell lines. RESULTS: Cell lines overexpressing HER-2eu showed higher proliferation when compared to low HER-2eu-expressing cell lines. Compared to low-expressing cell lines, high HER-2eu expressors were significantly more sensitive to patupilone than to paclitaxel (P<0.0002). In contrast, there was no appreciable difference in sensitivity to patupilone versus paclitaxel in primary USPC cell lines with low HER-2eu expression. Higher levels of beta-tubulin III (TUBB3) and P-glycoprotein (ABCB1) were detected in USPC cell lines with high versus low HER-2eu expression (P<0.05). CONCLUSIONS: USPC overexpressing HER-2eu display greater in vitro sensitivity to patupilone and higher levels of the patupilone molecular target TUBB3 when compared to low HER-2eu expressors. Due to the adverse prognosis associated with HER-2eu overexpression in USPC patients, patupilone may represent a promising novel drug to combine to platinum compounds in this subset of aggressive endometrial tumors.