Polyoxometalate SbW9 regulates proliferation and apoptosis of NSCLC cells via PTEN-dependent AKT signaling pathway.

Abstract

To explore the influence of polyoxometalate SbW9 on proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and its mechanism. NSCLC cell lines A549 and PC9 were treated with 50 μM polyoxometalate. Then, the proliferation of NSCLC cells was detected via 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-t tetrazolium hydroxide (XTT) assay and colony formation assay; the apoptosis of NSCLC cells was detected via flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); and the expression of apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax), was detected via Western blotting. Moreover, the protein expression levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN), phosphorylated-protein kinase B (P-AKT) and total AKT (T-AKT) were detected via Western blotting. The polyoxometalate inhibited the proliferation of A549 and PC9 cells in a concentration-dependent manner (5-100 μM) (p<0.05), and it (50 μM) also inhibited the proliferation of both cells in a time-dependent manner (0-72 h) (p<0.05). The results of colony formation assay revealed that the polyoxometalate (50 μM) could significantly inhibit the colony formation of A549 and PC9 cells (p<0.05). The results of flow cytometry and TUNEL staining showed that the polyoxometalate (50 μM) significantly induced the apoptosis of A549 and PC9 cells (p<0.05). According to further studies, the polyoxometalate (50 μM) inhibited the expression of anti-apoptotic gene Bcl-2 and promoted the expression of pro-apoptotic gene Bax. Besides, the Western blotting results manifested that the polyoxometalate could activate the expression of PTEN and inhibit the phosphorylation of downstream AKT (p<0.05). The polyoxometalate can activate the expression of PTEN to inhibit the phosphorylation of AKT, ultimately inhibiting the proliferation and inducing the apoptosis of NSCLC cells. Therefore, the polyoxometalate is expected to become a novel drug for the clinical treatment of NSCLC.