PMID- 31599421 OWN - NLM STAT- MEDLINE DCOM- 20201006 LR - 20211015 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 23 IP - 18 DP - 2019 Sep TI - Polyoxometalate SbW9 regulates proliferation and apoptosis of NSCLC cells via PTEN-dependent AKT signaling pathway. PG - 7959-7967 LID - 19012 [pii] LID - 10.26355/eurrev_201909_19012 [doi] AB - OBJECTIVE: To explore the influence of polyoxometalate SbW9 on proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and its mechanism. MATERIALS AND METHODS: NSCLC cell lines A549 and PC9 were treated with 50 muM 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. RESULTS: The polyoxometalate inhibited the proliferation of A549 and PC9 cells in a concentration-dependent manner (5-100 muM) (p<0.05), and it (50 muM) 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 muM) 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 muM) significantly induced the apoptosis of A549 and PC9 cells (p<0.05). According to further studies, the polyoxometalate (50 muM) 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). CONCLUSIONS: 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. FAU - Sun, H-B AU - Sun HB AD - Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China. xznjida@163.com. FAU - Xu, L AU - Xu L FAU - Wang, Z-X AU - Wang ZX FAU - Zheng, Y AU - Zheng Y FAU - Zhao, Y AU - Zhao Y FAU - Yin, Y-Y AU - Yin YY FAU - Han, X-L AU - Han XL FAU - Xu, Z-N AU - Xu ZN LA - eng PT - Journal Article PT - Retracted Publication PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (BAX protein, human) RN - 0 (BCL2 protein, human) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Tungsten Compounds) RN - 0 (bcl-2-Associated X Protein) RN - 9IT35J3UV3 (Antimony) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) SB - IM RIN - Eur Rev Med Pharmacol Sci. 2021 Apr;25(7):2825. PMID: 33877676 MH - A549 Cells MH - Antimony/*pharmacology MH - Apoptosis/*drug effects MH - Carcinoma, Non-Small-Cell Lung/*metabolism/pathology MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Humans MH - In Situ Nick-End Labeling MH - Lung Neoplasms/*metabolism/pathology MH - PTEN Phosphohydrolase/*drug effects/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/*drug effects/metabolism MH - Proto-Oncogene Proteins c-bcl-2/drug effects/metabolism MH - Tumor Stem Cell Assay MH - Tungsten Compounds/*pharmacology MH - bcl-2-Associated X Protein/drug effects/metabolism EDAT- 2019/10/11 06:00 MHDA- 2020/10/07 06:00 CRDT- 2019/10/11 06:00 PHST- 2019/10/11 06:00 [entrez] PHST- 2019/10/11 06:00 [pubmed] PHST- 2020/10/07 06:00 [medline] AID - 19012 [pii] AID - 10.26355/eurrev_201909_19012 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):7959-7967. doi: 10.26355/eurrev_201909_19012.