ABSTRACT
BACKGROUND: Interleukin-11 (IL-11) could promote invasion and metastasis of cancer cells, however, its mechanism is unclear. OBJECTIVE: This study aimed to investigate the effects of recombinant human IL-11 (rhIL-11) on lung cancer cell metastasis and growth. METHODS: Human lung cancer cell, A549, was cultured and subcutaneously injected into mice to establish Xenograft tumor models. Tumor models were divided into control, rhIL-11 transplantation (250 µg/kg/day), and rhIL-11 transplantation (500 µg/kg/day) group. Tumor volumes were recorded and measured 6 times. Hypoxia- Inducible Factor 1α (HIF1α), snail, slug, Signal Transducers/Activators of Transcription-3 (STAT3), E-cadherin, twist, and vimentin levels were evaluated using western blot and Real-Time PCR (RT-PCR). RESULTS: Sizes of subcutaneous tumors increased following measurement time. rhIL-11 treatment significantly enhanced HIF1α and STAT3 expression in rhIL-11 treatment groups compared to the control group (p<0.05). However, no remarkable differences were discovered between rhIL-11 (250 µg/kg/day) and rhIL-11 (500 µg/kg/day) group (p>0.05). rhIL-11 treatments significantly increased twist, and slug expressions compared to control group (p<0.05), especially for rhIL-11 (500 µg/kg/day) treatment, which triggered significantly higher effects on twist and slug expressions compared to those in the control group (p<0.05). Vimentin and snail mRNA levels were significantly up-regulated and E-cadherin level was significantly down-regulated in rhIL-11 treatment groups compared to the control group (p<0.05). Meanwhile, rhIL-11 at a dosage of 500 µg/kg/day triggered remarkably higher effects on vimentin, snail, and E-cadherin expressions compared to those in rhIL-11 (250 µg/kg/day) group (p<0.05). CONCLUSION: rhIL-11 transplantation promoted growth and Epithelial-Mesenchymal Transition (EMT) of A549 cells, which might be associated with STAT3/HIF-1α/EMT signaling pathway activation.
Subject(s)
Adenocarcinoma of Lung/therapy , Antineoplastic Agents/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Interleukin-11/metabolism , Lung Neoplasms/therapy , STAT3 Transcription Factor/metabolism , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Animals , Cell Proliferation , Drug Screening Assays, Antitumor , Epithelial-Mesenchymal Transition , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Recombinant Proteins/metabolism , Signal Transduction , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To evaluate the efficacy and adverse effects of weekly irinotecan combined with capecitabine as a second-line chemotherapy for treatment of advanced gastric cancer. METHODS: Twenty-one patients with advanced gastric cancer who had failed first-line therapy received irinotecan on days 1 and 8 plus capecitabine on days 1-14 for a 21-day cycle. Each patient was treated for at least two cycles and evaluated 4 weeks later for the responses. RESULTS: Of the 21 patients, none showed complete remission (CR), 5 (23.8%) showed partial remission (PR), 6 (28.6%) showed stable disease (SD) and 10 (47.6%) showed progressive disease (PD). The overall response rate was 23.8%, and 11 patients (52.4%) benefited (CR+PR+SD) from the clinical therapy, with a mean time to tumor progression of 3.61±0.97 months. The main adverse effects of this regimen included myelosuppression, nausea, vomiting and diarrhea. CONCLUSION: The regimen of weekly irinotecan plus capecitabine has a definite effect for treatment of advanced gastric cancer with tolerable toxicity.
