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BACKGROUND Sorafenib, a multiple-target-point kinase inhibitor, has been used as a standard treatment for advanced liver cancer and has shown therapeutic benefits. However, resistance often occurs, prompting the need for identification of synergizing agents. Celastrol is a major active ingredient of Tripterygium wilfordii, which can increase the antitumor effect of traditional antitumor drugs. This work focused on the sensitization of liver cancers in use of celastrol combined with sorafenib. MATERIAL AND METHODS The IC50 values of sorafenib and celastrol on cancer cells were determined through MTT assays. The effects of sorafenib on AKT signaling and VEGF levels in sorafenib-treated cancer cells were analyzed by Western blotting and ELISA, respectively. After combined treatment with celastrol and sorafenib, the survival rate of tumor cells was determined by MTT and clonogenic assays, and the apoptosis rate was also determined by flow cytometry. In addition, the in vivo antitumor activity of celastrol combined with sorafenib was evaluated in Hepa1-6 tumor-bearing mice. RESULTS Sorafenib treatment induced the compensatory activation of the AKT pathway and autocrine VEGF in hepatoma cells, which could be reversed by celastrol. Furthermore, celastrol enhanced the growth inhibition and apoptosis induction of cancer cells by sorafenib both in vitro and in vivo and reduced the dosage of sorafenib needed. CONCLUSIONS Celastrol enhances the antitumor activity of sorafenib in HCC tumor cells by suppressing the AKT pathway and VEGF autocrine system.

Objective: The immune makers including CD4+CD25+ T cells, natural killer cells, and T cells subgroup were retrospectively analyzed to find the relationship between apatinib and the immune system in the patients treated with apatinib. Method: Forty-two patients with advanced malignant tumors orally took apatinib as treatment and 16 patients with the same situation did not take apatinib as a control group. These patients were all included in the study, and they orally received apatinib 500 mg daily as monotherapy or combination. The treatment was continued until disease progression or intolerable toxicity. CD4+CD25+ T cells, natural killer cells, and T cells subgroup were detected before and 1 month after therapy for all the patients. The relationship between the changing number of immune cells and progression-free survival was analyzed in this study. Result: For the apatinib group, the rate of CD4+CD25+ T cells significantly increased ( P = .048). The median progression-free survival was 3.25 months for the 42 patients. The median progression-free survival in the patients with the rate of CD4+CD25+ T cells increased and decreased was 5.8 months and 2.9 months, respectively ( P = .012). Multivariate analysis found the increased rate of CD4+CD25+ T cells was an independent prognostic factor for a longer progression-free survival. The rate of natural killer cells and T cells subgroup did not change much after apatinib therapy, and they were not independent prognostic factors for progression-free survival. Conclusion: The rate of CD4+CD25+ T cells is very important in patients with apatinib treatment. The changing number of CD4+CD25+ T cells may be a good indicator for apatinib prognosis. Natural killer cells and T cells subgroup did not change much after apatinib, and they were not independent prognostic factors for progression-free survival.