Background: Autophagy plays a "double-edged sword" in the process of tumorigenesis, development and metastasis. Objective: In this study, we explored the effect of PI3K/AKT/mTOR autophagy related signaling pathway on regulating and controlling the invasion and metastasis of liver cancer cells by Bufalin. Methods: The cell counting , migration , adhesion and invasion assay were used to evaluate the effect of Bufalin on the cell proliferation, invasion and metastasis. The protein expression of PI3K/AKT/mTOR signaling pathway were detected by Western Blotting technique. Results: After inhibiting autophagy of HCC-LM3 cells, the inhibitory effect of Bufalin on adhesion, migration and invasion of HCC-LM3 cells was significantly enhanced. The synergistic inhibition was strongest when different autophagy inhibitors were combined with 3MA and CQ. After inhibiting autophagy, Bufalin significantly inhibited the protein expression of P-AKT, Cyclin D1, MMP-2, MMP-9 and VEGF in HCC-LM3 cells. The protein expression of PTEN and E-Cadherin in HCC-LM3 cells was significantly increased. Conclusion: The present study shows that the anti-tumor effect of Bufalin mainly inhibit the proliferation, extracellular matrix degradation and angiogenesis of HCC by influencing autophagy. These findings confirm the capability of Bufalin in inhibiting metastasis of HCC and in parallel to current patents could be applied as a novel therapeutic strategy in the prevention of metastasis of HCC.

PurposeGastric cancer, the cancer initiated from the stomach, is ranked as the third most frequent reason of cancer death worldwide. Gastric cancer-initiating cells (CICs) are one of the crucial causes for the metastasis and recurrence of gastric cancer, and CD44 is considered to be one marker for gastric CICs. Special AT-rich sequence binding protein 1 (SATB1) is a protein that promotes cancer progression, metastasis, and invasion and also participates in the maintenance of CICs. In this study, we investigated the therapeutic effect of SATB1 siRNA against gastric CICs and we constructed SATB1 siRNA-encapsulated immunoliposomes conjugated with CD44 antibodies (CD44-SATB1-ILs) to enhance the therapeutic effect of SATB1 siRNA against gastric CICs.MethodsWe investigated the therapeutic effect of the SATB1 suppression by SATB1 siRNA on CD44+ gastric CICs. CD44-SATB1-ILs were developed by the lyophilization/hydration approach. The targeting and cytotoxic effect of CD44-SATB1-ILs toward gastric CICs were evaluated in vitro.ResultsIn this study, for the first time, we confirmed that SATB1 suppression by SATB1 siRNA preferentially eliminated CD44+ gastric CICs. The results showed that CD44-SATB1-ILs could efficiently and specifically promote the SATB1 siRNA delivery to CD44+ gastric CICs, achieving superior therapeutic effects against CD44+ gastric CICs than non-targeted liposomes.ConclusionAs far as we know, our report is the first research that indicated the promotion of siRNA delivery via nanoparticles to gastric CICs and achievement of superior therapeutic effect against gastric CICs by utilization of CD44 antibody. Therefore, CD44-SATB1-ILs represent an up-and-coming approach for eliminating gastric CICs and also a promising treatment for therapy of gastric cancer.

Aim: USP22, a member of ubiquitin-specific proteases (USPs), is a well-defined protein that promotes poor prognosis, invasion and metastasis, and also participates in the maintenance of cancer stem cells. USP22 siRNA-loaded nanoliposomes conjugated with CD44 antibodies (USP22-NLs-CD44) were constructed to enhance the therapeutic effect of USP22 siRNA against gastric cancer stem cells. Materials & methods: The targeting and therapeutic efficacies of USP22-NLs-CD44 against gastric cancer stem cells were evaluated. Results & conclusion: USP22-NLs-CD44 was demonstrated to be able to effectively deliver USP22 siRNA to CD44+ gastric cancer stem cells, achieving superior therapeutic effects against CD44+ gastric cancer stem cells than nontargeted nanoliposomes. USP22-NLs-CD44 may provide a novel approach to eradicate gastric cancer stem cells in the near future.

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