Ginsenoside CK Inhibits TGF-β-Induced Epithelial-Mesenchymal Transition in A549 Cell via SIRT1

Ginsenoside CK is the main metabolite of protopanaxadiol saponins in intestinal bacteria. Previous studies have shown that ginsenoside CK can affect many aspects of tumor development through a variety of mechanisms. However, few studies have reported the antimetastatic effects of ginsenoside CK in non-small-cell lung cancer (NSCLC). In this study, we explored the effect of ginsenoside CK on epithelial-mesenchymal transition (EMT) induced by TGF-β in A549 cells and the potential molecular mechanisms. Our data showed that ginsenoside CK effectively prevented TGF-β-induced EMT, as indicated by the upregulation of E-cadherin and downregulation of vimentin. Furthermore, ginsenoside CK inhibited the metastatic ability of A549 cells in the tail vein lung metastasis model of nude mice. Additionally, ginsenoside CK decreased the expression of silent information regulator 2 homolog 1 (SIRT1) in the inhibition of EMT induced by TGF-β. Moreover, the antimetastatic effect of ginsenoside CK was reversed by SIRT1 overexpression. Generally, our results indicated the antimetastatic effect and underlying mechanism of ginsenoside CK on TGF-β-induced EMT in A549 cells, suggesting that ginsenoside CK can be used as an effective antineoplastic agent.

Inhibition of metastasis using particles that release chitosan upon radiation: A preliminary study

This study aimed to investigate the effect of the particles releasing chitosan upon exposure to radiation on inhibition of metastasis. A 10 mL solution of water containing 0.2% weight/volume alginate, 0.1% hyaluronic acid, and 100-mg chitosan was sprayed into the vibrating solution through a stainless mesh filter (pore size: 0.8 [Formula: see text]m) using an ultrasound disintegrator, thereby generating chitosan particles. Further, [Formula: see text] particles floating in 0.1 mL normal saline were subcutaneously injected around the 4TI cells-derived tumor in the left hind legs of six-week-old male C3He/N mice. Six hours after injection, tumors were exposed to 10 Gy or 20 Gy of 100-keV soft X-ray radiation. The release of chitosan was expressed as the frequency of ruptured chitosan particles 12 h after radiation. The antimetastatic effect was confirmed by a reduction in the number of metastatic pulmonary nodules 21 days after completion of treatment. More than [Formula: see text]% of the chitosan particles released chitosan in response to radiation. The particles releasing chitosan had a prolonged antimetastatic effect when compared with the particles not releasing chitosan, thereby resulting in a significantly greater antimetastatic effect lasting for four weeks since the completion of treatment, in tumors treated with both 10 Gy and 20 Gy of radiation. Hence, particlizing chitosan could be useful in reducing metastasis in irradiated tumors.

Targeting Toll-like receptor 4 with CLI-095 (TAK-242) enhances the antimetastatic effect of the estrogen receptor antagonist fulvestrant on non-small cell lung cancer

Purpose Estrogen plays a critical role in the invasiveness and metastasis of non-small cell lung cancer (NSCLC) through estrogen receptor β (ERβ). However, the antimetastatic effect of the ERβ antagonist fulvestrant was still limited in NSCLC patients. Recently, Toll-like receptor 4 (TLR4) signaling was implicated in NSCLC metastasis. Our present study aimed to evaluate the synergistic antimetastatic effect of a combination of fulvestrant and the TLR4-specific inhibitor CLI-095 (TAK-242) on human NSCLC cells. Methods The expression levels of ERβ and TLR4 were detected by immunohistochemical (IHC) analysis of 180 primary NSCLC and 30 corresponding metastatic lymph node samples. The association between ERβ and TLR4 expression was analyzed. The aggressiveness of NSCLC cells treated with fulvestrant, CLI-095 or the drug combination and formation status of their invadopodia, invasion-associated structures, were investigated. The protein levels in NSCLC cells in different groups were determined by Western blot and immunofluorescence analyses. Results Here, a positive correlation between ERβ and TLR4 expression was observed in both primary NSCLC tissue (Spearman’s Rho correlation coefficient = 0.411, p < 0.001) and metastatic lymph node tissue (Spearman’s Rho correlation coefficient = 0.374, p = 0.009). The protein levels of ERβ in NSCLC cell lines were decreased by fulvestrant, and this suppressive effect was significantly enhanced when fulvestrant was combined with CLI-095 (p < 0.05). Both the migration and invasion of NSCLC cells were suppressed by fulvestrant or CLI-095 alone, and the combination of fulvestrant + CLI-095 showed the strongest inhibitory effect (p < 0.05). In addition, the results demonstrated that CLI-095 also helped fulvestrant restrict the formation and function of invadopodia in NSCLC cells (p < 0.05). Conclusions Collectively, our study results suggested that CLI-095 enhances the antimetastatic effect of fulvestrant on NSCLC and provided support for further investigation of the antitumor activity of combined therapy with antiestrogen and anti-TLR4 agents in the clinic.