Cytokine CCL2 Induces Platinum-resistance In Gastric Cancer

Background and purposeChemotherapy is one of the most important approaches for the treatment of gastric cancer. However, tumor cells often develop resistance to chemotherapeutic drugs, leading to the failure of chemotherapy. It’s of great urgency to explore the mechanisms in hide. Our experiment aims to verify that the cytokine CCL2 autocrined by tumor cells can attenuate gastric tumor cell’s sensitivity to platinum and is resposible for the clinic drug-resistance to platinum-based chemotherapy.MethodsIn order to discover the relevant cytokine and testify its crucial role in developing drug-resistance, we took advantage of the platinum-sensitive and -resistant gastric cancer cell lines established before. Co-culture experiments、cytokine screening、gene knockout cytotoxicity assay and TUNEL assay are the key methods applied in this experiment.ResultsThe drug-resistant cells can transmit resistance to drug-sensitive cells with the mediation of autocrine cytokine, protecting the drug-sensitive cells from the platinum induced apoptosis. CCL2 upregulation is screened by the cytokine antibody array and further confirmed by ELSIA assay. Knocking-out CCL2 gene by siRNA can restore the sensitivity of drug-resistant gastric cancer cells to platinum. And vise versa, the drug-sensitive cells finally develop drug-resistance after the addition of exogenous CCL2. Conclusionwe come to the conclusion that gastric tumor cells can reduce the level of apoptosis by upregulating the cytokine CCL2 and eventually leading to platinum-resistance.