Oridonin Improves the Therapeutic Effect of Lentinan on Lung Cancer

Abstract

Oridonin, a compound from Rabdosia rubescens, has been shown to have a potency for the improvement of the antitumor effect of lentinan (LNT). In this study, we tested the effect of oridonin, LNT, and the combination of them on a normal human fetal lung fibroblast cell line MRC-5 and non-small cell lung cancer cell line A549. Then we tested their effects on metastasis and survival with a lung cancer mice model. The effects of them on the mRNA and protein expression of several regulatory factors in A549 and lung tissue were determined by QPCR and western blotting. Results showed that the viability of MRC-5 and A549 were not affected by 0-20 µg/ml oridonin. 0-300 µg/ml LNT did not affect the viability of MRC-5, but 50-400 µg/ml LNT inhibited the viability of A549. 20 µg/ml oridonin and 100 or 300 µg/ml LNT were used in the subsequent study. The oridonin, LNT, or the combination of both had no effect on MRC-5 cell viability. The oridonin had no effect on A549 cell viability but LNT suppressed A549 cell viability, and oridonin promoted the suppression of LNT on A549 cells. In vivo study showed that oridonin alone had no effect on metastasis and survival but LNT decreased metastasis and survival in mice. Oridonin improved the suppression of LNT against metastasis and further improved the survival rate. In both A549 and lung tissues, LNT increased the mRNA and protein expression of caspase-3, caspase-8, caspase-9, Bax, p53, p21, and IκB-α, reduced mRNA and protein expressions of Bcl-2 and NF-κB. Oridonin enhanced all the effects of LNT on cells. Our study demonstrated that oridonin enhanced the antitumor effects of LNT and is conducive to the development of oridonin and LNT as a novel cancer drug regimen.