Gang Liang

OBJECTIVE: To examine the influence of Saponin I from Shuitianqi ( Rhizoma Schizocapasae Plantagineae) ) (SSPH I) on hepatocellular carcinoma (HCC) metastasis, and to elucidate the underlying mechanism. METHODS: The intrahepatic metastasis Bagg's Albino/c (BALB/c) mouse model was established with human hepatocellular carcinomas (HepG2) cells, then treated with normal saline (once per day), cisplatin (2 mg/kg, once every 2 d), and SSPH I (25, 50, and 75 mg/kg, once per day). Then, we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology techniques. RESULTS: Based on our analysis, SSPH I significantly alleviated hepatocyte necrosis and tumor cells infiltration. Moreover, SSPH I suppressed extracellular matrix (ECM) degradation and angiogenesis via a decrease in matrix etalloproteinase-2 (MMP-2), MMP-9, CD31, CD34, and vascular endothelial growth factor (VEGF) levels. Furthermore, SSPH I repressed invasion and metastasis by suppressing the transforming growth factor-131 (TGF- 13 1)/Smad7 axis and epithelial-mesenchymal transition (EMT), as evidenced by the scarce TGF-beta 1, Ncadherin, and Vimentin expressions, and elevated Smad7 and E-cadherin expressions. CONCLUSION: The SSPH I-mediated negative regulation of the TGF- 13 1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

Fighting against tumors is an ongoing challenge in both medicinal and clinical applications. In recent years, chemotherapy, along with surgery, has significantly improved the situation to prolong life expectancy. Theoretically, and regardless of dosage, we now have drugs that are strong enough to eliminate most tumors. However, due to uncontrollable drug distribution in the body, it is difficult to increase treatment efficiency by simply increasing dosages. For this reason, the need for a drug delivery system that can release “bombs” at the target organ or tissue as precisely as possible has elicited the interest of researchers. In our work, we design and construct a silica-based nanocomposite to meet the above demand. The novel nanocomposite drug carrier can be guided to target tumors or tissue by a magnetic field, since it is constructed with superparamagnetic Fe₃O₄ as the core. The Fe₃O₄ core is clad in a mesoporous silica molecular sieve MCM-41 (represented as MS, in this article), since this MS has enormous ordered hexagonal caves providing sufficient space to hold the drug molecules. To modify the magnetically guided carriers so that they become both magnetically guided and light-responsive, benzophenone hydrazone is coupled into the molecular sieve tunnel. When a certain wavelength of light is imposed on the gating molecules, C=N double bonds vibrate and swing, causing the cavity that holds the drug molecules to change size and open the tunnels. Hence, the nanocomposite has the ability to release loaded drugs with light irradiation. The structure, loading abilities, and the size of the nanocomposite are inspected with a scanning electron microscope, a transmission electron microscope, thermogravimetry analysis, N₂ adsorption/desorption, and dynamic light scattering The biocompatibility and in vitro drug molecule controlled release are tested with an SMMC-7721 cell line.

Introduction: Saponin of Schizocapsa plantaginea Hance I (SSPH I), a novel bioactive phytochemical isolated from the rhizomes of Schizocapsa plantaginea, has been demonstrated to exhibit anti-cancer activity against various tumors in preclinical studies. However, the molecular mechanisms involved in the suppression of hepatocellular carcinoma (HCC) are poorly understood. The present study aimed at analyzing the effects of SSPH I on autophagy and apoptosis in vitro. Methods: MTT and colony forming assays were used to detect cell viability and cell proliferation. Hoechst 33,258 staining and flow cytometry were used to determine apoptosis and ROS production. The apoptosis and autophagy-related protein expression levels were evaluated via Western blot assay. Characteristics of autophagy and apoptosis were observed by transmission electron microscopy. Lysosomal activity was stained with Lyso-Tracker Red and Magic Red Cathepsin B. Results: The results showed that SSPH I exhibited potent anti-cancer activity and proliferation in HepG2 and BEL-7402 cells and inhibited HepG2 cells through inhibiting autophagy and promoting apoptosis. The mechanistic study indicated that the inhibition of autophagy of SSPH I was mediated by blocking autophagosome–lysosome fusion. Additionally, we found that SSPH I could mediate the activation of MAPK/ERK1/2 signaling pathway, and the use of NAC (ROS inhibitor) and U0126 (MEK1/2 inhibitor) converted the effect of SSPH I on apoptosis and autophagy in HepG2 cells. Conclusion: These data suggest that SSPH I induces tumor cells apoptosis and reduces autophagy in vitro by inducing ROS and activating MAPK/ERK1/2 signaling pathway, indicating that SSPH I might be a novel agent for the treatment of HCC.

Oral squamous cell carcinoma (OSCC) is a very aggressive malignancy, and 50% of patients who receive curative treatment die from the disease or related complications within 5 years. Epigallocatechin‐3‐gallate (EGCG) is the most abundant bioactive ingredient of tea polyphenols in green tea and has anticancer properties. Here, we evaluated the preclinical efficacy of EGCG combined with vincristine sulfate (VCR) on the growth, angiogenic activity and vascular endothelial growth factor (VEGF) expression in xenograft nude mice inoculated with KBV200 cells. Compared with VCR alone, the combined use of EGCG and VCR strongly inhibited tumour growth and angiogenesis ( P < 0.01). VEGF mRNA and protein levels were lower in the KBV200 xenograft group treated with the combined regime ( P < 0.01) than those in the VCR alone group. EGCG sensitises multidrug‐resistant OSCC to VCR, and this may occur through the inhibition of angiogenesis via VEGF down‐regulation.