Oridonin improves the therapeutic effect of lentinan on lung cancer

Oridonin, a compound from Rabdosia rubescens, has been shown to exhibit a potent ability to improve the antitumor effects of lentinan (LNT). In the present study, the effects of oridonin, LNT, and the combination of these treatments were assessed on the normal human fetal lung fibroblast cell line MRC-5, as well as the non-small cell lung cancer cell line A549. Next, their effects on metastasis and survival in vivo were assessed in a mouse model of lung cancer. The effects of the treatments on the mRNA and protein expression levels of several regulatory factors in A549 cells and lung tissues were determined using reverse transcription-quantitative PCR and western blotting. The results showed that the viability of MRC-5 and A549 cells were not affected by 0-20 µg/ml oridonin; 0-300 µg/ml LNT did not affect the viability of MRC-5 cells, but 50-400 µg/ml LNT reduced the viability of A549 cells. Thus, 20 µg/ml oridonin and 100 or 300 µg/ml LNT were used in the subsequent experiments. Treatment with oridonin and LNT, alone or combined, had no effect on MRC-5 cell viability. Oridonin treatment had no effect on A549 cell viability; however, LNT suppressed A549 cell viability, and oridonin promoted the suppressive effects of LNT on A549 cells. In vivo analysis showed that oridonin alone had no effect on metastasis and survival, but LNT decreased metastasis and survival in mice. Oridonin augmented the effects of LNT against metastasis and further improved the survival rates of mice. In both A549 cells and lung tissues, LNT increased the mRNA and protein expression levels of caspase-3, caspase-8, caspase-9, Bax, p53, p21 and inhibitor of nuclear factor-κB (NF-κB)-α, and reduced the mRNA and protein expression levels of Bcl-2 and NF-κB. Oridonin augmented all the effects of LNT on expression of these proteins in the cells. Together, the results showed that oridonin enhanced the antitumor effects of LNT, and may thus serve as an adjuvant alongside LNT as a novel anticancer regimen for treatment of lung cancer.