β-Elemene against human lung cancer via up-regulation of P53 protein expression to promote the release of exosome.

β-Elemene, a novel antitumor plant drug extracted from the traditional Chinese medicinal herb Zedoary, has been shown to be effective against a wide variety of tumors. Recent studies have indicated that β-elemene can inhibit the growth of lung cancer cells; however, the exact mechanism of β-element's action in lung cancer remains largely unknown. In the present study, the antitumor effect of β-elemene on human lung cancer cells and the mechanism involved has been investigated.

The inhibitory effects of β-elemene on cell growth were measured by Trypan Blue exclusion and MTT assay. Flow cytometric analysis was used to detect the cells' apoptotic rate. The expression of P53 mRNA and protein were measured by RT-PCR and Western blot analysis, respectively. Exosomes were isolated by differential centrifugation steps and analyzed by electron microscopy and western blotting. P53 knockdown cells were established through transfection with P53 siRNA. To investigate the effect of β-elemene on the tumor growth in vivo, a Xenograft nude mouse model was established by injecting the A549 cells into the back of a BABL/c nude mouse.

β-Elemene markedly inhibited growth and induced apoptosis in lung cancer cells. The levels of the anti-apoptotic genes Bcl-2 and Bcl-xl in A549 cells decreased, while expression of P53 and production of exosomes increased after β-elemene treatment. Further siRNA studies suggested that the effect of β-elemene on A549 cells is dependent on P53 expression. Exosomes derived from A549 cultured with a human lung cancer cell line exhibited decreased tumor cell proliferation. The in vivo study demonstrated that β-elemene inhibited tumor growth, and up-regulated the expression of P53 and the release of exosome.

Our results demonstrated β-elemene acts on lung cancer cells in a P53 dependent manner and exosomes are involved in the regulation of cell proliferation.