Wentilactone A induces cell apoptosis by targeting AKR1C1 gene via the IGF‑1R/IRS1/PI3K/AKT/Nrf2/FLIP/Caspase‑3 signaling pathway in small cell lung cancer

Jiang,Wenli; Meng,Linghong; Xu,Guangming; Lv,Cuiting; Wang,Hongliang; Tian,He; Chen,Ruohua; Jiao,Binghua; Wang,Bingui; Huang,Caiguo

doi:10.3892/ol.2018.9486

Wentilactone A induces cell apoptosis by targeting AKR1C1 gene via the IGF‑1R/IRS1/PI3K/AKT/Nrf2/FLIP/Caspase‑3 signaling pathway in small cell lung cancer

Authors:
- Wenli Jiang
- Linghong Meng
- Guangming Xu
- Cuiting Lv
- Hongliang Wang
- He Tian
- Ruohua Chen
- Binghua Jiao
- Bingui Wang
- Caiguo Huang
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Affiliations: Department of Biochemistry and Molecular Biology, The Faculty of Basic Medical Science, Second Military Medical University, Shanghai 200433, P.R. China, Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Key Laboratory of Experimental Marine Biology, Institute of Oceanology of The Chinese Academy of Sciences, Qingdao, Shandong 266071, P.R. China, College of Pharmacy, Shanghai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of Pediatrics, Shanghai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of VIP Clinical, Shanghai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
Published online on: September 24, 2018 https://doi.org/10.3892/ol.2018.9486
Pages: 6445-6457
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Wentilactone A (WA), a marine‑derived compound, inhibits proliferation of NCI‑H446, as demonstrated by previous research; however, the anti‑SCLC mechanism underlying WA was not fully investigated. The present study aimed to investigate the anti‑SCLC mechanism underlying WA in vitro and in vivo. Cell Counting Kit‑8 was used to assay cell growth, flow cytometry was conducted to analyze cell apoptosis and nude mice xenografts were used to examine SCLC growth following WA treatment. Bioinformatics was used for verification of the target gene of WA. Reverse transcription‑quantitative polymerase chain reaction and western blot were used to examine aldo‑keto reductase family 1 member C1 (AKR1C1) mRNA and protein levels, and AKR1C1‑associated proteins prior to and following WA treatment. Cell growth, apoptosis and growth of nude mice xenografts were assayed prior to and following transfection with AKR1C1 knockdown or overexpression carriers, respectively. It was determined that AKR1C1 was a target gene of WA. Decreased AKR1C1 expression and WA treatment promoted apoptosis in SCLC via the insulin like growth factor‑1 receptor/insulin receptor substrate 1/phosphoinositide 3‑kinase/AKT/nuclear factor‑erythroid 2‑associated factor 2/Fas‑associated death domain‑like interleukin‑1‑converting enzyme‑like inhibitory protein/Caspase‑3 pathway. WA attenuated the proliferation and induced the apoptosis of SCLC cells in vitro and in vivo by targeting the AKR1C1 gene. WA may be a novel AKR1C1‑targeted drug candidate for the treatment of SCLC in the future.

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