Gemcitabine （GEM） is a cell-cycle specific inhibitor of DNA synthesis and repair, and has been applied as the first-line therapy for patients with locally advanced or metastatic pancreatic cancers. However, the medi...Gemcitabine （GEM） is a cell-cycle specific inhibitor of DNA synthesis and repair, and has been applied as the first-line therapy for patients with locally advanced or metastatic pancreatic cancers. However, the median survival time is only 5.65 mon when GEM was administrated as a monothearpy. Therefore, novel therapeutic agents and/or combinations with GEM are needed for the treatment of pancreatic cancer. In this study, we aim to evaluate the efficacy of treatment with wbselen （WB）, GEM, and combination treatment with GEM and WB in two pancreatic cancer cell lines, JF305 and MiaPaCa-2 cells. The combination index （CI） and the dose-reduction index （DRI） of combined treatment with different dose and time regimes were analyzed based on median-effect theory. Compared with single treatment with GEM, combination treatment displayed decreased response time and IC 50 , and increased maximum inhibition. Among the different combination regimes, the most significant synergistic effect was achieved when the dose ratios of WB to GEM was 2：1 in JF305 cells and 1：1 in MiaPaCa-2 cells after 48 h of drug treatment. When combinations of WB and GEM were used in these two cell lines, the dose of GEM was significantly reduced while the total drug concentration increased, especially after 48 h of drug treatments. Our results indicated that the combination treatment with WB and GEM had synergistic effect against pancreatic cancer in vitro.展开更多
文摘Gemcitabine （GEM） is a cell-cycle specific inhibitor of DNA synthesis and repair, and has been applied as the first-line therapy for patients with locally advanced or metastatic pancreatic cancers. However, the median survival time is only 5.65 mon when GEM was administrated as a monothearpy. Therefore, novel therapeutic agents and/or combinations with GEM are needed for the treatment of pancreatic cancer. In this study, we aim to evaluate the efficacy of treatment with wbselen （WB）, GEM, and combination treatment with GEM and WB in two pancreatic cancer cell lines, JF305 and MiaPaCa-2 cells. The combination index （CI） and the dose-reduction index （DRI） of combined treatment with different dose and time regimes were analyzed based on median-effect theory. Compared with single treatment with GEM, combination treatment displayed decreased response time and IC 50 , and increased maximum inhibition. Among the different combination regimes, the most significant synergistic effect was achieved when the dose ratios of WB to GEM was 2：1 in JF305 cells and 1：1 in MiaPaCa-2 cells after 48 h of drug treatment. When combinations of WB and GEM were used in these two cell lines, the dose of GEM was significantly reduced while the total drug concentration increased, especially after 48 h of drug treatments. Our results indicated that the combination treatment with WB and GEM had synergistic effect against pancreatic cancer in vitro.
