Ginsenoside Rb1 Antagonist Dasatinib-induced Inhibition on NK Cells Cytotoxicity to Ovarian Cancer Cells

OBJECTIVE To analyze the inhibiting effects of dasatinib on natural killer(NK) cells cytotoxicity on ovarian cancer cell and explore the antagonistic effects of ginsenoside Rb1 on dasatinib-induced immunosuppression effects. METHODS The NK cells were pre-treated with dasatinib, ginsenoside Rb1 and dasatinib combined with ginsenoside Rb1, respectively. The NK cells with no drug pretreatment were carried out as control. CFSE/PI double staining was used to measure the death rate of ovarian cancer cell HO-8910 cells after co-culturing with NK cells; Annexin V-FITC/PI staining was used to detect the vitality of NK cells; real-time PCR was applied to evaluate the mRNA level of granzyme B and Western-blotting was used to detect the phosphorylation levels of ERK. RESULTS Compared with the non-pretreated NK cells, the transcription levels of granzyme B, phosphorylation levels of ERK and the cytotoxicity were significantly down-regulated in dasatinib-treated NK cells (P<0.01). Compared with dasatinib treated NK cells, pre-treated in the combination of dasatinib and ginsenoside Rb1, the transcriptional levels of granzyme B, pERK and cytotoxicity of NK cells were elevated(P<0.05). However, the levels of transcriptional granzyme B, pERK and cytotoxicity of NK cells between ginsenoside Rb1 treated group and control group showed no significant difference(P<0.05). CONCLUSION Dasatinib has inhibiting effects on the cytotoxicity of NK cells by decreasing the amount of granzyme B, one of the crucial cytotoxic molecules in NK cells and inhibiting phosphorylation of ERK which is crucial for NK cells reactivity. Though ginsenoside Rb1 can’t activate NK cells directly, it has antagonistic effects on dasatinib-induced immunosuppression of NK cells. It suggests that the combination use of ginsenoside Rb1 and dasatinib can decrease the suppression effects of dasatinib on NK cells.