Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. However, whether or not OP-B has any potential antitumor activity has not been reported. Here, we show that the non-small cell lung cancer (NSCLC) cell lines NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles in their cytoplasm compared to untreated control cells. Flow cytometric analysis showed that the cells were arrested in G0/G1 phase. Nuclear morphology, Annexin-V/PI staining, and expression of cleaved caspase-3 all confirm that OP-B does not induce apoptosis. Instead, based on results from both transmission electron microscopy (TEM) and the expression of microtubule-associated protein 1 light chain 3-II (LC3-II), we determined that OP-B treatment induced autophagy in both cell lines. Next, we examined the PI3K/Akt/mTOR signaling pathway and found that OP-B inhibited phosphorylation of Akt (Ser473, Thr308) in NCI-H157 cells and also inhibited several key components of the pathway in NCI-H460 cells, such as p-Akt(Ser473, Thr308), p-p70S6K (Thr389). Additionally, insulin-mediated activation of the PI3K/Akt/mTOR pathway provides evidence that activation of this pathway may correlate with induction of autophagy in H460 cells. Therefore, OP-B is a prospective inhibitor of PI3K/Akt and may be used as an alternative compound to treat NSCLC.

Aim of the study. In recent years, the incidence of lung cancer, as well as the mortality rate from this disease, has increased. Moreover, because of acquired drug resistance and adverse side effects, the effectiveness of current therapeutics used for the treatment of lung cancer has decreased significantly. Chinese medicine has been shown to have significant antitumor effects and is increasingly being used for the treatment of cancer. However, as the mechanisms of action for many Chinese medicines are undefined, the application of Chinese medicine for the treatment of cancer is limited. The formula tested has been used clinically by the China National Traditional Chinese Medicine Master, Professor Zhonging Zhou for treatment of cancer. In this article, we examine the efficacy of Ke formula in the treatment of non-small cell lung cancer and elucidate its mechanism of action. Methods. A Balb/c nude mouse xenograft model using A549 cells was previously established. The mice were randomly divided into normal, mock, Ke, cisplatin (DDP), and co-formulated (Ke + DDP) groups. After 15 days of drug administration, the animals were sacrificed, body weight and tumor volume were recorded, and the tumor-inhibiting rate was calculated. A cancer pathway finder polymerase chain reaction array was used to monitor the expression of 88 genes in tumor tissue samples. The potential antiproliferation mechanism was also investigated by Western blot analysis. Results. Ke formula minimized chemotherapy-related weight loss in tumor-bearing mice without exhibiting distinct toxicity. Ke formula also inhibited tumor growth, which was associated with the downregulation of genes in the PI3K/AKT, MAPK, and WNT/β-catenin pathways. The results from Western blot analyses further indicated that Ke blocked the cell cycle progression at the G1/S phase and induced apoptosis mainly via the PI3K/AKT pathway. Conclusion. Ke formula inhibits tumor growth in an A549 xenograft mouse model with no obvious side effects. Moreover, Ke exhibits synergistic antitumor effects when combined with DDP. The mechanism of action of Ke is to induce cell cycle arrest and apoptosis by suppressing the PI3K/AKT pathway. Further research will be required to determine the mechanism of action behind the synergistic effect of Ke and DDP.

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