CDDO-Me inhibits tumor growth and prevents recurrence of pancreatic ductal adenocarcinoma
| Autor: | Xiaohua Gao, Subhash C. Gautam, Dorrah Deeb, Yiguan Zhang, Yongbo Liu, Patricia Liu, Jiajiu Shaw |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Akt/mTOR/NF-κB signaling
Cancer Research Pathology medicine.medical_specialty endocrine system diseases Blotting Western Cell pancreatic ductal adenocarcinoma Antineoplastic Agents Mice SCID Biology CDDO-Me Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Humans Oleanolic Acid Cell Proliferation 030304 developmental biology 0303 health sciences Oncogene Cell growth apoptosis Cancer Articles Cell cycle medicine.disease Xenograft Model Antitumor Assays 3. Good health Pancreatic Neoplasms medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis residual disease Cancer research Female Neoplasm Recurrence Local Carcinoma Pancreatic Ductal |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2015.3212 |
| Popis: | Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) has shown potent antitumorigenic activity against a wide range of cancer cell lines in vitro and inhibited the growth of liver, lung and prostate cancer in vivo. In the present study, we examined the antitumor activity of CDDO-Me for pancreatic ductal adenocarcinoma (PDAC) cells with and without activating K-ras mutations. Treatment of K-ras mutant MiaPaCa-2 and K-ras normal BxPC-3 cells with CDDO-Me elicited strong antiproliferative and proapop-topic responses in both cell lines in culture. The inhibition of cell proliferation and induction of apoptosis was accompanied by the inhibition of antiapoptotic/prosurvival p-Akt, NF-κB and p-mTOR signaling proteins. For testing efficacy of CDDO-Me in vivo heterotopic and orthotopic xenografts were generated by implanting BxPC-3 and MiaPaCa-2 cells subcutaneously and in the pancreatic tail, respectively. Treatment with CDDO-Me significantly inhibited the growth of BxPC-3 xenografts and reduced the levels of p-Akt and p-mTOR in tumor tissue. In mice with orthotopic MiaPaCa-2 xenografts, treatment with CDDO-Me prolonged the survival of mice when administered following the surgical resection of tumors. The latter was attributed to the eradication of residual PDAC remaining after resection of tumors. These preclinical data demonstrate the potential of CDDO-Me for treating primary PDAC tumors and for preventing relapse/recurrence through the destruction of residual disease. |
| Databáze: | OpenAIRE |
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