Apoptosis of small cell lung cancer cells H1688 and H446 induced by nitidine chloride through PI3K/Akt/Bcl-2/caspase-3/PARP pathway / 中国药理学通报

ABSTRACT

Aim To explore the apoptosis of small eell lung eancer ( SCLC ) eells HI688 and H446 induced by nitidine chloride and its possible mechanism.Methods The effect of nitidine chloride or cisplatin ( DDP ) on the activity of SCLC cells was detected by j J MTT method; the morphological changes of cells trea¬ted with nitidine chloride or DDP were observed by in- verted fluorescence microscope and HE staining; the effect of nitidine chloride or DDP on apoptosis was de¬tected by flow cytometry; the effect of apoptosis inhibi¬tor Z-VAD-FMK on apoptosis induced by nitidine chlo¬ride or DDP was detected by MTT method.The expres¬sions of Bax , Bcl-2, caspase-3 , PARP, p-PI3K and p- Akt in the cells treated with nitidine chloride or DDP were detected by Western blot.Results MTT results showed that the viability of SCLC cells was significantly reduced after 48 hours of treatment with nitidine chlo¬ ride; compared with DDP, nitidine chloride could in¬hibit SCLC cells with less IC50; inverted fluorescence microscope and HE staining showed that nitidine chlo¬ride could induce apoptosis in SCLC cells, similar to DDP; flow cytometry showed that nitidine chloride J J could induce apoptosis in SCLC cells.The results of MTT assay showed that the inhibitory effect of nitidine chloride on apoptosis of SCLC cells could be partially antagonized by apoptosis inhibitor Z-VAD-FMK.West¬ern blot results showed that, similar to DDP, nitidine chloride could inhibit the expression of PI3K and Akt, increase Bax, inhibit Be 1-2, and promote the cleavage of caspase-3 and PAH P.Conclusion Nitidine chlo¬ride can induce apoptosis of SCLC cells by inhibiting the activation of P13K and Akt.