Astragaloside IV sensitizes non–small cell lung cancer cells to gefitinib potentially via regulation of SIRT6

Abstract

Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse biological roles including the antitumor activity. In this study, we evaluated the chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell Counting Kit-8 analysis was performed to determine cell viability. Real-time polymerase chain reaction and western blot were used to measure the messenger RNA and protein expression. Results showed that astragaloside IV treatment could suppress the proliferation of non-small cell lung cancer cells. In addition, combined treatment with astragaloside IV remarkably enhanced the chemosensitivity to gefitinib in three non-small cell lung cancer cell lines including NCI-H1299, HCC827, and A549. Furthermore, compared with gefitinib-treated cells, the messenger RNA expression of SIRT6 was obviously increased in non-small cell lung cancer cells treated with gefitinib combined with astragaloside IV. In addition, downregulation of SIRT6 was accomplished using small interference RNA technology. As a result, SIRT6 inhibition abolished the sensitization role of astragaloside IV in non-small cell lung cancer cells. Taken together, these data demonstrated that astragaloside IV sensitized tumor cells to gefitinib via regulation of SIRT6, suggesting that astragaloside IV may serve as potential therapeutic approach for lung cancer.

Antimetastasis Effect of Astragalus membranaceus-Curcuma zedoaria via β-Catenin Mediated CXCR4 and EMT Signaling Pathway in HCT116

“…Some researchers reported that CXCR4 is regulated by Wnt/ β -catenin pathway and key factors in EMT pathway are also regulated by β -catenin related ways. Astragaloside IV, an active component in Astragalus membranaceus, and β -elemene, an active component in Curcuma zedoaria, are reported to attenuate the Wnt/ β -catenin pathway by previous reporters [14, 27]. These results are in accordance with our results that decrease the degradation of the β -catenin rescuing the HCT116 from HQEZ.…”

“…Astragalus membranaceus is a traditional Chinese medicine widely used in cancer therapy. It is thought that Astragalus membranaceus restore the immune functions in cancer patients, and some natural components from Astragalus membranaceus enhanced chemosensitivity or inhibited cancer cells directly [14–16]. Astragalus membranaceus also protects patients during chemotherapy against liver damage as well as nervous system damage, especially against platinum-derived toxicity [17, 18].…”

Downregulation of SIRT6 by miR-34c-5p is associated with poor prognosis and promotes colon cancer proliferation through inhibiting apoptosis via the JAK2/STAT3 signaling pathway

“…Decreased expression of SIRT6 promotes tumor cell growth and is closely correlated with the poor prognosis of ovarian cancer, gastric cancer and glioma ( 20 , 25 , 32 ). In non-small cell lung cancer, SIRT6 can suppress cell proliferation via the inhibition of Twist1, and astragaloside IV can sensitize non-small cell lung cancer cells to gefitinib by upregulating SIRT6 ( 33 , 34 ). However, some studies have reported opposite findings.…”

Astragaloside III Enhances Anti-Tumor Response of NK Cells by Elevating NKG2D and IFN-γ

“…Several Chinese herbs have been used for treatment of cancer in ancient China, and Astragalosides belong to one class of these agents (Yan et al, 2017). Compounds from Astragaloside, such as Astragaloside II and IV, have been characterized with broad-spectrum antitumor activities (Cheng et al, 2014; Zhang et al, 2014; Dai et al, 2017; Hu et al, 2017; Jiang et al, 2017; Yan et al, 2017). However, the anti-tumor effect of Astragaloside III, an important constituent of Astragaloside, is largely unknown.…”