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- W2028374439 abstract "Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILT-type Ca2+ channel mediated Ca2+ influx is important for tumor cell proliferation. In order to understand the role of this influx in tumor cell cycling, we conducted experiments to block T-type calcium channels in MCF7 breast cancer cells using pharmacological inhibitors, mibefradil or its more T-type calcium channel specific derivative NNC-55-0396, and examined the effects of this blockade on the passage through the cell cycle of MCF7 cells and whether T-type calcium channel inhibition can be used in conjunction with paclitaxel chemotherapy to increase the efficacy of the chemotherapy. Flow cytometry shows that blocking T-type calcium channels with the specific inhibitor NNC-55-0396 resulted in an increase in MCF7 cells in the G1 phase and a decrease in cells in the S phase of the cell cycle. Treatment with paclitaxel for 72 hours in vitro yielded lower MCF7 cell numbers than treatment with NNC-55-0396, as measured by a cell proliferation assay. However, a treatment regimen alternating NNC-55-0396 with paclitaxel over 72 hours was found to reduce MCF7 cell number to a larger degree than either agent alone for the same time period. For in vivo modeling, MCF7 xenografts were implanted in the mammary fat pads of nude mice, with tumor size monitored via caliper measurements. Similar to the in vitro findings, a treatment regiment that alternated paclitaxel chemotherapy with the calcium channel inhibitor mibefradil reduced tumor size to a larger degree than either agent alone, though that difference did not rise to a statistically significant level. These results indicate that blocking T-type calcium channels halts proliferating MCF7 cells at the G1/S checkpoint, and that this phenomenon may lead to an increased sensitivity to paclitaxel chemotherapy.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5672. doi:1538-7445.AM2012-5672" @default.
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- W2028374439 date "2012-04-15" @default.
- W2028374439 modified "2023-09-25" @default.
- W2028374439 title "Abstract 5672: Mibefradil increases paclitaxel's effect on MCF-7 cell proliferationin vitroandin vivo" @default.
- W2028374439 doi "https://doi.org/10.1158/1538-7445.am2012-5672" @default.
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