Comparison of chemotherapy sensitivity of different breast cancer cell lines and investigation of potantial mechanisms

Breast cancer is one of the most common and deadly cancers in women. Treatment strategies change depending on molecular subtypes and metastasis status. Standard treatment options for breast cancer patients include surgery, chemotherapy, hormonal treatment, immunotherapy and radiotherapy. Although most patients respond to initial treatment in a relatively short time, most patients ultimately experience chemoresistance, leading to therapeutic failure. Therefore, many studies were carried out to better understand chemoresistance in order to improve chemotherapy and the management of breast cancer. Most frequently used cell lines in these studies are MCF-7 and MDA-MB-231. MCF-7 cell line corresponds to ER (estrogen receptor)- and PR (progesterone receptor)-positive breast cancer which belongs to luminal A molecular subtype and it has low invasion and metastasis potential. ER-positive breast cancer is the most common subtype of breast cancer and its treatment includes interventions to target ER or to limit estrogen production. MDA-MB-231 cell line is a triple negative breast cancer cell line which does not have ER, PR and HER2 expression, and therefore it is highly aggressive, invasive and poorly differentiated. In this study, the cytotoxic effect of several chemotherapy agents such as Cisplatin, Epirubicin, 5-Fluorouracil, Vorinostat and 5-Aza-2dC was determined by MTT assays in order to reveal the differences in chemotherapy sensitivity between both breast cancer cell lines. We also tested protein and mRNA expression levels of two members of the TNF receptor family, 4-1BBL and OX40L, which are known as important molecules for T cell responses following treatment with an immunogenic agent, bortezomib by using flow cytometry and qRT-PCR. Our findings revealded that the chemotherapy agents used showed different cytotoxic effects in both cell lines, while proteosome inhibition was observed to have a potential immunogenic effect by increasing the expression levels of 4-1BBL and OX40L, specifically in the MDA-MB-231 cell line. As a result, we have come up with the idea that recommending a treatment modality depending on the molecular phenotype in breast cancer treatment will provide more clinical success.