Apatinib and Ginsenoside-Rb1 Synergetically Control the Growth of Hypopharyngeal Carcinoma Cells

Abstract

Background. Apatinib is an anticancer drug known to inhibit the vascular endothelial growth factor receptor-2 (VEGFR-2) through regulating tyrosine kinases. Drug resistance and reduced activity in various cancers is the matter of great concern; thus, researchers opt to use combination of the two or more drugs. So far, its gynergetic anticancer role with a traditional Chinese drug Ginsenoside-Rb1 (G-Rb1) has not been studied in cancers including hypopharyngeal carcinoma. Objective. The current study is aimed at investigating the anticancer synergetic effects of G-Rb1 and apatinib in hypopharyngeal carcinoma. Methods. The synergetic effects of both drugs on cell proliferation, wound healing and cell migration, and cell apoptosis were studied in hypopharyngeal carcinoma cells. Furthermore, the xenograft rat model was generated, and tumor inhibition was monitored after treating rats with both drugs as mono- and combination therapy. In addition, protein expression and localization were performed by western blotting and immunofluorescent staining, respectively. Results. The analyses of the data showed that combination therapy of apatinib and G-Rb1 significantly inhibited the proliferation, migration, and wound healing capability of hypopharyngeal carcinoma cells. Moreover, the glycolysis rate of the cells in the combination therapy (apatinib and G-Rb1) group was significantly decreased as compared to that in the monotherapy group or no treatment group, suggesting that the glycolysis inhibition led to the inhibition of tumor growth. Moreover, the combination therapy on xenograft rats dramatically reduced the tumor size. Furthermore, combination therapy also exhibited an increased count of CD3+ and CD4+ T cells, as well as the ratio between CD4+ and CD8+ T cells. Conclusion. Interestingly, a combination of apatinib and G-Rb1 induced more tumor cell apoptosis and reduced cell proliferation than the individual drug treatment and promote antitumor immunity by enhancing immunomodulatory molecules. Thus, we believe that this study could serve as a valuable platform to assess the synergetic anticancer effects of the herbal as well as synthetic medicines.

Integrating Chinese medicine into mainstream cancer therapies: a promising future

“…GRb1 increased the intracellular drug concentration of cisplatin by targeting ABCB1 and the Hedgehog pathway, reversing cisplatin resistance in A549/DDP cells and improving its efficacy (15). In nasopharyngeal carcinoma cells, Li et al reported that GRb1 combined with apatinib could inhibit tumor cell glycolysis, reduce tumor cell proliferation and migration, upregulate the immune-related indices CD3 + and CD4 + , increase apoptosis, enhance the expression of immune regulatory molecules, and exert synergistic anticancer effects on nasopharyngeal carcinoma cells via ginsenosides to inhibit the malignant progression of nasopharyngeal carcinoma (16). In cervical cancer chemotherapy, paclitaxel (PTX) resistance has become a major challenge and therapeutic difficulty.…”

Research Progress on Anti‐Inflammatory Mechanisms of Black Ginseng

“…Ginsenoside Rb1 combined with apatinib can significantly increase the levels of CD3 + and CD4 + cells and the proportion of CD4 + to CD8 + cells It has stronger immunomodulatory activity than single-use treatment. [37] Rb1 alone can improve proliferation, inflammation, and adipogenesis induced by TNF-α treatment of adipocytes, and when combined with berberine (BBR), which has the same efficacy, it has a synergistic protective effect on TNF-α-induced inflammation in adipocytes by inhibiting the NF-кB signaling pathway. [38] Ginsenosides and polysaccharides can regulate the expression of T cell receptors (TCR) and mediate the activation of T lymphocytes.…”

“…Active substances in black ginseng can improve the activity of T cells and enhance the immune response through synergistic effects with other drugs. Ginsenoside Rb1 combined with apatinib can significantly increase the levels of CD3 + and CD4 + cells and the proportion of CD4+ to CD8+ cells It has stronger immunomodulatory activity than single‐use treatment [37] . Rb1 alone can improve proliferation, inflammation, and adipogenesis induced by TNF‐α treatment of adipocytes, and when combined with berberine (BBR), which has the same efficacy, it has a synergistic protective effect on TNF‐α‐induced inflammation in adipocytes by inhibiting the NF‐κB signaling pathway [38] …”

Anti-cancer effect and potential microRNAs targets of ginsenosides against breast cancer

“…Recently, studies have confirmed that ginsenosides can be used in combination with a variety of drugs to enhance the inhibitory effect on cancer cells or increase the sensitivity to traditional chemotherapy drugs ( Choi et al, 2013 ). For example, ginsenoside Rb1 and apatinib work synergistically to enhance the inhibition of growth of pharyngeal cancer cells ( Li Y. et al, 2022 ). Combination therapy of ginsenoside Rg3 and chemotherapeutics drugs against BC has been demonstrated.…”