Paper Title
Preclinical Evaluation of Synthetic Inhibitors Target Dual Proteins for Ovarian Cancer Therapy

Abstract
Recently, American Cancer Society estimated that new ovarian cancer cases exceeded 22 thousand including 14 thousand expected death case. Clinically, the standard chemotherapy drugs used to treat patients with ovarian cancer are combination of a platinum-based drug such as carboplatin or cisplatin with a taxane such as paclitaxel or docetaxel. These drugs used to treat patients with this disease show undesirable drug resistance after the initial promising treatment. Therefore, the development of new drugs is urgently required to enhance the drug pharmacological activity and to reduce the drug's side effects. The nimesulide drug is used as a starting material to synthesize a series of analogs, which have anticancer effect. These compounds target Heat shock protein27 (HSP27) because of its important cellular functions in the cell and it is up-regulated in cancer cells. HSP27 plays a role in tumor cell proliferation, differentiation, invasion, metastasis, and death. This study also provides the involvement of HER2, which is a trans-membrane protein tyrosine kinase receptor. HER2 is regulated by HSP27 through kinase phosphorylation and over-expression of HER2 is associated with a malignant phenotype in many cancers, including ovarian cancer. The goal of this study is to find ovarian cancer cell line that is highly expressing HER2 and then test the nimesulide analogs toxicity effect on these cell lines to select the potent agents that target dual proteins through HER2 pathway.