Anti-tumor activity of tanshinone IIA in combined with cyclophosphamide against Lewis mice with lung cancer

Abstract

Objective: To explore the anti-tumor activity of tanshinone IIA in combined with cyclophosphamide against Lewis mice with lung cancer and the effect on cellular immune function.

Methods: Lewis tumor cells were inoculated subcutaneously into the right armpit of mice in each group (n = 20) to establish Lewis lung cancer mice model. After model establishment, mice in the model group were given normal saline by lavage, qd. Mice in treatment I group were given intraperitoneal injection of Tan IIA, 15 mg/kg, qd. Mice in treatment II group were given intraperitoneal injection of CTX, 25 mg/kg, qd. Mice in treatment III group were given intraperitoneal injections of Tan IIA and CTX, in which the administration method of Tan IIA was the same as in treatment I group, continuously for 2 weeks, and the dosage of CTX was the same as in treatment II group, 24 h after model establishment, every other day. Mice were sacrificed 2 weeks after establishment. The tumor tissues were collected to calculate the anti-tumor rate. Immunohistochemistry was used to detect the expressions of Bcl-2, Bax, VEGF, Angiostatin, and Endostatin. FCM was used to detect T lymphocyte subsets in spleen and liver of mice.

Results: The tumor weight in treatment I, II, and III groups was significantly lower than that in the model group (P < 0.05). The tumor weight in treatment III group was significantly lower than that in treatment I and II groups (P < 0.05). The anti-tumor rate in treatment II and III groups was significantly higher than that in treatment I group (P < 0.05). Bcl-2 expression in the tumor tissues of treatment I, II, and III groups was significantly lower than that in the model group (P < 0.05), while Bax expression was significantly higher than that in the model group (P < 0.05). Bcl-2 expression in the tumor tissues of treatment I and II groups was significantly higher than that in treatment III group (P < 0.05), while Bax expression was significantly lower than that in treatment III group (P < 0.05). CD4⁺ and CD4⁺/CD8⁺ in treatment I, II, and III groups were significantly higher than those in the model group (P < 0.05). CD4⁺ in treatment III group was significantly higher than that in treatment I and II groups (P < 0.05), while CD4⁺/CD8⁺ was significantly higher than that in treatment II group (P < 0.05). The comparison of CD8⁺ among each group was not statistically significant (P > 0.05). NK cell activity in treatment I, II, and III groups was significantly higher than that in the model group (P < 0.05). NK cell activity in treatment III group was significantly higher than that in treatment I and II groups (P < 0.05).

Conclusions: Tan IIA in combined with CTX can down regulate Bcl-2 expression in lung cancer tissues, up regulate Bax expression, inhibit the neovascularization of tumor tissues, and enhance the immunological function, with a significant anti-tumor activity.

Keywords: Angiostatin; Bax; Bcl-2; Endostatin; Lung cancer; VEGF.