The anti-tumor effect and underlying mechanism of micheliolide on H460 lung cancer by notch4 signal pathway / 医学研究生学报

ABSTRACT

Objective Previous studies have found that micheliolide(MCL) could improve the sensitivity of breast cancer cells to chemotherapeutic drugs such as cisplatin and induce the apoptosis of breast cancer cells.This article aims to study the proliferation inhibition effect of micheliolide on lung cancer cells H460 and its underlying mechanism.Methods Human lung cancer cell line H460 was treated with different concentrations of micheliolide(30,60,90μmol/L).Then the cell proliferation was measured by-CCK8 and plate colony formation assays.The apoptosis and the cell cycle were detected by flow cytometry.Western blot was used to determine the mechanism of how MCL affecting cancer cell H460.Results Compared with the control (275.00±7.21), the clone numbers after 30μmol/L,60μmol/L and 90μmol/L MCL treatment(199.00±5.66,166.00±1.41, 90.00±7.81) were significantly decreased (P<0.05).Meanwhile, the CCK-8 results showed that compared to the control group, A value was significantly increased after 30μmol/L MCL treatment for 72h and 96h, and 60μmol/L or 90μmol/L MCL treatment for 48h,72h and 96 h (P<0.05).Compared with the control apoptotic ratio [(2.90±0.03)％], the ratio of early and late apoptotic cells after 30μmol/L, 60μmol/L and 90μmol/L MCL treatment [(5.23±0.76)％, (9.06±0.47)％, (19.00±0.64)％] were significantly increased (P<0.05).Compared with the control group, the ratio of G2/M phase cells[(12.52±0.88) ％ ,(17.22±0.43)％, (19.84±0.31)％] was gradually increased after 30μmol/L, 60μmol/L and 90μmol/L MCL treatment, and there was statistically significant difference after 60μmol/L and 90μmol/L MCL treatment (P<0.05).The ratio of S+G1/G0 phase cells[(87.53±1.06)％ ,(82.94±0.67)％ ,(79.79±0.21)％] was gradually decreased after 30μmol/L, 60μmol/L and 90μmol/L MCL treatment, and there was statistically significant difference after 60μmol/L and 90μmol/L MCL treatment (P<0.05).The expression level of notch4 was significantly decreased after 30μmol/L, 60μmol/L and 90μmol/L MCL treatment (P<0.05), while the expression level of cleaved caspase3 was significantly upregulated (P<0.05).Conclusion MCL exerted an inhibitory effect on lung cancer cell H460.