Cinobufacini Injection Suppresses the Proliferation of Human Osteosarcoma Cells by Inhibiting PI3K/Akt Signaling Pathway

Background: Cinobufacini injection (CI), an aqueous extraction from the Cutis Bufonis, is broadly used in clinical treatment of cancer in China. However, the underlying molecular mechanisms of CI in treating osteosarcoma (OS) remain unclear. Aberrant activation of PI3K-AKT signaling pathway is the cause of many types of cancer, including OS. Therefore, we investigated the effect of CI on proliferation, apoptosis and cell cycle of OS cells and elucidated the molecular mechanism of CI in inhibiting OS cells. Methods: Cell proliferation of U2OS and MG63 cells after CI treatment was measured by CCK-8 assay, colony formation and morphological changes. Additionally, the cell cycle arrest and apoptosis induced by CI, were determined by FACS and Western blot analysis. The mechanisms of CI on OS were evaluated by RNA-seq and Western blot analysis. Results: We founf that CI reduced the proliferation of U2OS and MG63 cells in a dose- and time- dependent manner. Furthermore, CI induced the U2OS cells cycle arrest in G0/G1 phase, but the MG63 cells cycle arrest in G2/M phase. Consequently, CI triggered the apoptosis in both OS cells, with enhanced caspase-3 activity and decreased expression of Bcl-2/Bax. In addition, RNA-seq data indicated that PI3K-Akt signaling pathway played an essential role in CI treatment. Moreover PI3K and phosphorylation of AKT (p-AKT) were significantly down-regulated by CI in both OS cells. Conclusions: These results indicate that CI significantly inhibited the proliferation, induced the cell cycle arrest, as well as apoptosis in human OS cells, which is mediated by the inactivation of PI3K-Akt signaling pathway. These findings suggest that CI may have potential for the treatment of OS.

Cinobufacini Injection Improves the Efficacy of Chemotherapy on Advanced Stage Gastric Cancer: A Systemic Review and Meta-Analysis

Gastric cancer has a high morbidity and mortality. Chemotherapy regimens are routine advanced stage gastric cancer (AGC) treatment protocols, but most of these drugs have side-effects such as myelosuppression and gastrointestinal disorders. Cinobufacini, an extractive from TCM, could suppress cell proliferation and inhibit gastric cancer. In this study, we comprehensively reviewed the literature on the efficacy comparison between Cinobufacini injection combined with chemotherapy and chemotherapy solely used in AGC treatment. We extracted data for from six electronic databases to evaluate the efficacy of Cinobufacini injection on AGC patients. Twelve studies with a total of 853 patients were finally included in our study. The results indicated that Cinobufacini injection could increase response rate and disease control rate of chemotherapy on AGC, improve the life quality of AGC patients, increase leukocytes, improve anemia, improve hand-foot syndrome induced by chemotherapy, and relieve cancer pain. This study has its own limitations that prevented us from drawing a definite conclusion and more well-designed clinical trials of TCM are needed.

Treatment of Huge Hepatocellular Carcinoma Using Cinobufacini Injection in Transarterial Chemoembolization: A Retrospective Study

The aim of this study is to examine the safety and efficacy of Cinobufacini injection in transarterial chemoembolization (TACE) for treatment of huge hepatocellular carcinoma (HCC). Clinical data of 56 consecutive patients with HCC larger than 10 cm who had been treated with TACE between December 2010 and August 2014 were retrospectively analyzed. Among these patients, 31 belonged to the Cinobufacini group and 25 belonged to the epirubicin group. The clinical efficacy, survival time, and adverse events in patients in the two groups were compared. The objective response rate in the Cinobufacini group was significantly higher than that in the epirubicin group (53.6% versus 23.1%,P=0.022). The median survival time (10.6 versus 14.1 months,χ2=0.092,P=0.762) and the median time to progression (4.9 versus 5.7 months,χ2=0.097,P=0.756) were similar between the groups. The incidence rate of adverse events was lower in the Cinobufacini group than in the epirubicin group (P<0.05). The short-term clinical efficacy of Cinobufacini is better than that of epirubicin in TACE for treating huge HCC, while their long-term clinical efficacy is similar. However, lower incidence of adverse events was noted in TACE using Cinobufacini rather than epirubicin.

Effects of cinobufacini injection on hepatocarcinoma cell proliferation, invasion and metastasis

Background & aims: to explore the effects of Cinobufacini Injection (CI) on proliferation and invasion of hepatocarcinoma cells cultured with lymphatic endothelial cells (LECs), and lymphatic metastasis inhibition in immunocompetent mice.