| Chemotherapy is the main strategy in the treatment of cancer, cisplatin is one of the most common drugs used in cancer chemotherapy. However, the development of drug-resistance is the obstacle in long-term treatment of malignant neoplasm. Recently, accumulating evidence suggests that micro RNAs are involved in various bioactivities in oncogenesis. It is not unexpected that micro RNAs play a key role in acquiring of drug-resistance in the progression of tumor. Studies anticipated that more than two-thirds of human cancers can be prevented by foods and diet manipulation, vegetables, fruits, dietary fiber, and certain micronutrients have potential anticancer aproperties, especially bioactive lupeol, it has attracted interest due to its antioxidant, apoptosis inducing, antiprolifeative, antimutagenic and anti-inflammatory properties. At present, the role of micro RNAs in tumor drug resistance has gradually been revealed, at the same time, inhibition mechanism of lupeol in tumor cells also need to constantly improved. Therefore, the study of micro RNAs expression profiles induced by lupeol in drug-resistant cancer cells has certain significance for cancer treatment, but also to further improve the anti-tumor mechanism lupeol.In this research, we induced and maintained four levels of cisplatin-resistant He La cell lines(He La/CR1, He La/CR2, He La/CR3 and He La/CR4), detected their drug-resistance ability and mimic the development of drug-resistance in He La cells. According to the previous studies and exiting evidence, we selected five micro RNAs(mi R-183, mi R-182, mi R-30 a, mi R-15 b and mi R-16) and their potential target m RNAs as our research targets. The real-time RT-PCR was used to detect the relative expression of micro RNAs and their m RNAs. And then, the selected high drug-resistant He La cell line was treated in different time(6h, 12 h, 18 h and 24h) using lupeol, detected the relative expression level of candidate micro RNAs and their target by RT-PCR, and last, analyzed the possible signal pathway involved in micro RNAs induced by lupeol.The results showed that mi R-182 and mi R-15 b were up-regulated in resistant cell lines while mi R-183 and mi R-30 a were significantly down-regulated, KIAA1199 and PDCD4 is the target of mi R-183 and mi R-182 respective, but the target of mi R-30 a needs more studies. At the same time, the targets they regulated are related to the drug-resistance. The expression alteration of selected micro RNAs in resistant cell lines compared to their parent He La cell line suggests that He La cell drug resistance is associated with distinct micro RNAs, which indicates that micro RNAs may be one of the therapy targets in the treatment of cervical cancer by sensitizing cell to chemotherapy. The results acquired after luprol treatment show that the micro RNAs altered significantly, suggesting that the lupeol may through regulating the expression of micro RNAs and achieve the purpose of inhibiting tumor, at the same time, micro RNAs may become a new the target during the cancer therapy.In accordance with published results, we further deducted the downstream pathways and relative signal moleculars in cisplatin-resistant He La cells, in which there are Wnt/β-catenin, PI3K/PTEN/AKT, BAX, YB-1, NF-κB, Caspase family, PGRMC1, ATG and TGF-TGF-β, and can conclude that lupeol takes part in tumor inhibition by suppressing tumor cell proliferation, promoting apoptosis, restaining migration, and sensitizing cancer cells after chemotherapy through multiple targets and pathways. |
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