Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF‐β/Smad signaling pathway

Abstract

Objective To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV. Methods MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins. Results AS‐IV reduced the proliferation of SW962 cells in a concentration‐ and time‐dependent manner, induced cell‐cycle arresting in G0/G1 phase, as demonstrated by the up‐regulation of P53 and P21 expression, and the down‐regulation of cyclin D1 expression. AS‐IV enhanced the expression of Bax and cleaved‐caspase 3, and suppressed Bcl‐2 and Bcl‐xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin‐1 and LC3‐B was upregulated and that of P62 was downregulated, which suggested that AS‐IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3‐methyladenine (3‐MA), cell apoptosis decreased upon AS‐IV treatment. Similarly, TGF‐β1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF‐βRII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS‐IV treatment, the expression levels of the above proteins exhibited the opposite effect. Conclusion AS‐IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF‐β/Smad signaling pathway in VSCC.

Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity

“…Accordingly, the combination of vanadium and the traditional chemotherapy drug carboplatin induces a more potent G0/G1 cell cycle arrest [ 167 ]. Similarly, astragaloside IV also achieves cancer treatment via TGF-β-induced cell cycle arrest in the G0/G1 phase in vulvar squamous cell carcinoma, which enhanced cancer cell apoptosis simultaneously by increasing the expression of apoptotic genes including cleaved caspase-3 [ 168 ]. Meanwhile, heteronemin, a natural compound extracted from marine sponges, can reduce the expression of TGF-β1 and intercellular adhesion molecule 1, and inhibits cancer cell adhesion, motility, and proliferation in the bile duct cancer, cholangiocarcinoma [ 169 ].…”

BZW1 promotes cell proliferation in prostate cancer by regulating TGF-β1/Smad pathway

“…To explore the potential mechanism of BZW1, TGF-β1/Smad pathway was investigated. It is well known that TGFβ/Smad pathway is involved in cell proliferation [19][20][21]. Results shown that BZW1 over-expression activated the TGF-β1/Smad pathway.…”

Molecular mechanisms of astragaloside‑IV in cancer therapy (Review)

“…SMAd and downstream TGF-β intracellular signaling transfer the ligand-receptor interaction signal from the cytoplasm to the nucleus. In a previous study, in VScc cells, AS-IV was shown to improve the dysfunctions of the TGF-β/SMAd pathway, determined based on the elevated TGF-βRII and Smad4 levels; it was also found that AS-IV induced autophagy in SW962 cells, and markedly increased Beclin-1 and Lc3-II levels, and decreased p62 protein levels (19).…”

“…However, Bcl-2 can inhibit the release of cyt c and avoid the intrinsic apoptosis induced by Bax (15). Research has indicated that AS-IV can enhance the Bax/Bcl-2 ratio to induce intrinsic apoptosis in a number of types of cancer, including colorectal cancer (cRc), breast cancer, lung cancer, vulvar squamous cell cancer (VScc) and hepatocellular carcinoma (Hcc) (16)(17)(18)(19)(20)(21).…”