beta-elemene and Kidney-Neoplasms

Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. β-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated.. Human RCC 786-0 cells were treated with different concentrations of β-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy.. β-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that β-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with β-elemene. Combined treatment of β-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects.. Our data provide first evidence that β-elemene can inhibit the proliferation of RCC 786- 0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of β -elemene on 786-0 cells.

Topics: Adenine; Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Survival; Chloroquine; Extracellular Signal-Regulated MAP Kinases; Humans; Kidney Neoplasms; MAP Kinase Signaling System; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Sesquiterpenes; TOR Serine-Threonine Kinases

To investigate the curative effect and mechanism of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits.. The rabbits were all transplanted with VX2 carcinoma on kidney. Fifty-five rabbits were randomly divided into 11 groups. Rabbits in these groups were administered interventional treatment of normal saline, iodinated oil, mitomycin, 5-fluorouracil, beta-elemene, cisplatin, carboplatin, adriamycin, thiotepa, cyclophopsphamide, and vincristine, respectively. After corresponding intervention, the tumor volume in each group was measured by ultrasonography and spiral computed tomography, and the tumor growth rate (TGR) was calculated. Nenal and hepatic functions of the rabbits in each group were compared 1 day, 7 and 14 days after the interventional treatment. Morphologic change of the tumor was observed by a light microscopy and a transmission electron microscopy 14 days after interventional treatment. The expressions of Bax and Bcl-2 were measured by immunohistochemical straining.. There was statistical significance in the effects of different medicines intervened on VX2 kidney transplanted carcinoma. The VX2 carcinoma of rabbits had high-sensitivity to iodized oil embolism, mitomycin, cisplatin and carboplatin, which showed serious damage to the kidney function, medium-sensitivity to beta-elemene, adriamycin and 5-fluorouracil, in which beta-elemene showed slight damage to the kidney function, and resistance to thiotepa, cyclohosphamide and vincristine. Most tumor cells displayed apoptosis in the beta-elemene interventional treatment group under light microscopy and transmission electron microscopy, and only few tumor cells displayed necrosis. The Bax expression was up-regulated (P<0.05) and the Bcl-2 expression had no significant difference (P>0.05) in the beta-elemene interventional treatment group.. Intervention treatment of beta-elemene has significant effect on VX2 kidney transplanted carcinoma and little side effect on the kidney function. Its mechanism is related to enhancing the apoptosis of tumor cells, and Bax gene participates in this action.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; bcl-2-Associated X Protein; Chemoembolization, Therapeutic; Female; Immunohistochemistry; Injections, Intra-Arterial; Kidney; Kidney Neoplasms; Male; Microscopy, Electron; Neoplasm Transplantation; Phytotherapy; Proto-Oncogene Proteins c-bcl-2; Rabbits; Random Allocation; Sesquiterpenes