Investigation of chemotherapeutic sensitivity of breast cancer cells metastasized to different organs

Chemotherapy has an important role in breast cancer treatment. Resistance to chemotherapeutics is the most commonly encountered problem in the clinical oncology. This resistance can develop during primary treatment or can be acquired after the treatment regimen. In this study, we aimed to find out the most effective drug against breast cancer cells metastasized to different organs. As the candidate drugs, methotrexate, vinorelbine and cisplatin were selected as these drugs are currently under clinical use. All of the chemotherapeutics were used as single agent and the treatments were applied for 72 hours at different doses. By this way, the influence of different drug doses on the in vitro proliferation rates of metastatic breast cancer cell lines 4THM, 4TBM, 4TLM and the parental cell line 4T1, and the possible cytotoxic effects were investigated. In order to reveal the resistance mechanisms, western blotting against survivin protein was made for the resistant cell lines. According to our results, methotrexate is the most effective drug against 4TBM and 4TLM cell lines, while vinorelbine is the most effective drug against 4THM cell line. There was no significant difference in the sensitivity of 4T1 cells to either methotrexate or vinorelbine. Methotrexate, when used at high doses (10µM) was effective against both 4TBM and 4THM cells. Similarly, high doses of cisplatin killed 4TBM cells and high dose vinorelbine was effective against 4T1 cells. Treatment with 10nM cisplatin increased surviving expression in 4TLM cells while the expression levels of the same protein was found to be decreased in 4THM and 4TBM cells. 100nM methotrexate was sufficient to decrease survivin expression levels in 4T1, 4THM and 4TBM cell lines although survivin expression was not found to be changed in 4TLM cells. Vinorelbine, on the other hand, did not change the survivin expression levels in any of the cell lines investigated. Key Words: methotrexate, vinorelbine, cisplatin, surviving, metastatic breast cancer.