Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway
| Autor: | Chengyi Sun, Zhehao Liu, Liwen Chen, Zili Chen, Yiping Kang, Qianfan Liu, Ding'an Zhou, Xinhao Huang, Yuntao Guo, Zhu Haitao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
erlotinib Cancer Research Combination therapy medicine.medical_treatment pancreatic cancer Intraperitoneal injection Mice Nude Apoptosis Deoxycytidine JAK-STAT pathway Erlotinib Hydrochloride Mice 03 medical and health sciences 0302 clinical medicine Pancreatic cancer Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans Cell Proliferation Oncogene business.industry gemcitabine Cancer Articles Janus Kinase 1 General Medicine medicine.disease Xenograft Model Antitumor Assays Gemcitabine Pancreatic Neoplasms STAT Transcription Factors 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Female Erlotinib Neoplasm Recurrence Local business Ex vivo medicine.drug |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2018.6198 |
| Popis: | Compared to single gemcitabine treatment, the combination of gemcitabine and erlotinib has shown effective response in patients with locally advanced or metastatic pancreatic cancer. However, the combination therapy has not proven effective in patients with pancreatic cancer after R0 or R1 resection. In the present study, a nude mice model of orthotopic xenotransplantation after tumor resection was established using pancreatic cancer cell lines, BxPC-3 and PANC‑1. Mice were divided in four groups (each with n=12) and were treated as follows: the control group received a placebo via intraperitoneal injection (i.p.), while the other three groups were treated with gemcitabine (50 mg/kg i.p., twice a week), erlotinib (50 mg/kg oral gavage, once every three days), and combined treatment of gemcitabine and erlotinib, respectively. The treatment lasted for 21 days, after which all mice were sacrificed and tumors were examined ex vivo. We determined that the combination of gemcitabine and erlotinib inhibited recurrent tumor growth and induced apoptosis in vivo by downregulating phosphorylation levels of JAKs and STATs, which in turn downregulated the downstream proteins HIF‑1α and cyclin D1, and upregulated caspase‑9 and caspase‑3 expression. To sum up, the combination of gemcitabine with erlotinib was effective in treating patients with pancreatic cancer after R0 or R1 resection. |
| Databáze: | OpenAIRE |
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