Astrocyte elevated gene-1 (AEG-1) shRNA sensitizes Huaier polysaccharide (HP)-induced anti-metastatic potency via inactivating downstream P13K/Akt pathway as well as augmenting cell-mediated immune response

Abstract

Astrocyte elevated gene-1 (AEG-1) is an important force in the development and progression of hepatocellular carcinoma (HCC). To extend our study, we examined here the role of AEG-1 in anti-metastatic effects of Huaier polysaccharide (HP) on the human HCC MHCC97-H cell line. AEG-1 shRNA contributed to the anti-proliferation effect of HP on MHCC97-H cells. Furthermore, results of Transwell insert chambers showed that low expression of AEG-1 could effectively facilitate HP to suppress MHCC97-H cell migration and invasion. We achieved this by reducing phosphoinositide 3-kinases (P13K) and phosphorylated Akt (pAkt) expression as well as enhancing natural killer (NK) cell activity. Taken together, our data strongly suggested that AEG-1 shRNA could block the carcinogenesis and progression of MHCC97-H cells and highlight the therapeutic potential of HP in HCC treatment, at least by part, by inhibiting the activation of the PI3K/Akt pathway and enhancing the NK cell-mediated immune response. These findings may provide a new strategy for HCC treatment.

Huaier polysaccharide induces apoptosis in hepatocellular carcinoma cells through p38 MAPK

“…However, upon treatment with the specific MAPK inhibitors PD98059, SP600125 and SB203580 (targeting MEK, JNK and p38 MAPK, respectively), it was observed that the inactivation of p38 MAPK markedly antagonized the effect of HP-induced apoptosis and inhibition of proliferation in both HepG2 and Huh7 cells, indicating that p38 MAPK may play a role in the process of apoptosis. The present results also revealed that HP diminished the phosphorylation levels of AKT and mTOR, which is consistent with previous findings reported for HP-treated ovarian cancer cells and MHCC97-H cells (13,16).…”

“…Recent studies have noticed that Huaier polysaccharide (HP) exerts a pro-apoptotic effect on the cells of a variety of human cancers, including breast cancer (9,10), hepatocarcinoma (11)(12)(13)(14), lung adenocarcinoma (15) and ovarian cancer (16). In addition, Huaier and HP suppress cancer cell metastasis and motility (12,16,17), exhibit anti-angiogenic activity and enhance the host immune system function (11,14,18).…”

“…Although several studies indicated that HP induces apoptosis in HCC cells via different signaling pathways (13,19), the detailed mechanism by which this drug inhibits HCC cell growth remains to be explored.…”

The anticancer effect of Huaier (Review)

“…It was reported that W-NTRP significantly enhanced macrophage phagocytosis, increasing NO production and iNOS activity (16). An increased quantity of NK cells and enhanced NK cell activity were detected after exposure to Huaier polysaccharide (18,78). Huaier polysaccharide (TP-1) also modulated the cytokine release, as confirmed by the increased IFN-γ and IL-2 expression and inhibition of IL-10 expression.…”

“…However, the anticancer effects of Huaier which have attracted increasing worldwide interest have only been researched in recent years (14)(15)(16). Accumulating evidence suggests that the anticancer mechanisms of Huaier effects may be associated with various biological activities, such as inhibition of cell proliferation (15), anti-metastasis (17), interference with tumor angiogenesis (14) and tumor-specific immunomodulatory effect (16,18). Huaier was found to be a putative anticancer agent with broad therapeutic value following elaborate molecular studies conducted in the recent past.…”