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In-vitro evaluation of HSP27 inhibitors function through HER2 pathway for ovarian cancer therapy

Background: Heat shock protein 27 (HSP27) and human epidermal growth factor receptor 2 (HER2) are both attractive molecular targets for cancer therapy because of their cellular functions, which are proportionally up and down regulated in cancer cells. Previously, we synthesized a series of compounds known as HSP27 inhibitors using a nimesulide drug as a lead compound. Therefore, our hypothesis is to target HSP27 with inhibitors to stabilize HER2 receptor through HER2 pathway and reduce its expression. Methods: Three ovarian cancer cell lines (OVCAR3, SKOV3, and HEY1B) tested for HER2 over-expression by western blot assay and their cell growth inhibition were determined by the standard MTT assay. Results: Our findings using western blot assay revealed that SKOV3 cell line is an HER2 over-expression ovarian cancer cell line. In addition, the IC50 data from MTT assay also proved that SKOV3 cell line adapted cell growth inhibition. Overall, the data indicated that down regulation of HSP27 in SKOV3 cells stabilized HER2 receptor expression through HER2 pathway. 
 Conclusions: The development of series of anticancer agents that inhibit dual proteins may overcome the chemotherapy drug resistance and improve the survival of future ovarian cancer patients.