The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mcl-1 through a PI 3-K/Akt pathway

Wei, Lin-Hung; Kuo, Min-Liang; Chen, Chi-An; Chou, Chia-Hung; Cheng, Wen; Chang, M.-C.; Su, Jen Liang; Hsieh, Ching-Liang

doi:10.1038/sj.onc.1204733

Cited by 153 publications

(138 citation statements)

References 43 publications

(37 reference statements)

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“…This was unexpected because in cervical cancer patients in situ the STAT3 activation is weak or absent (10). This is in contrast to other malignancies, where STAT3 is constitutively active and is a considered anti-apoptotic factor (13)(14)(15).…”

Section: Introductionmentioning

confidence: 53%

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

et al. 2018

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Abstract. Cervical cancer stage-dependent therapies include surgery, chemotherapy, radiotherapy and chemoradiotherapy. Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard therapy for locally advanced cervical carcinoma (FIGO>IIB), however therapy resistance in a subset of patients is still a major clinical challenge. The present study aimed to analyze the impact of Oncostatin M (OSM) stimulation on CCRT-induced cell death. The present study used cells derived from cervical squamous cell carcinomas (SW756, 808, CaSki and 879) and adenocarcinoma (HeLa). The cervical carcinoma cells were HPV18-positive (HeLa, SW756, 808) or HPV16-positive (CaSki, 879). In addition to the established cell lines HeLa, SW756 and CaSki, the more recently generated cervical cancer cells 808 and 879 were also used. To analyze their radiosensitivity, cells were treated with increasing doses of irradiation (0-8 Gy). To mimic chemotherapy, radiotherapy or CCRT in vitro, the cells were challenged with 0.975 µg/ml cisplatin, irradiated with 6 Gy or a combination. A total of 10 ng/ml OSM was applied for 2 h prior to the respective therapy. The responsiveness toward radiation alone varied among the cervical carcinoma cells. CaSki, 808 and 879 cells were resistant to irradiation up to 8 Gy. OSM pre-treatment sensitized two out of five cell lines (HeLa and 879) to irradiation. Notably, all tested cells were sensitized by OSM for CCRT-treatment, particularly in the less radiosensitive cells. Cell death enhancement was dependent on phosphorylated signal transducer and activator of transcription 3 (STAT3; Tyr705) signaling activation as demonstrated with a dominant-negative version of STAT3 interfering with phosphorylation at Tyr705 (dnSTAT3-Y705F). In conclusion, OSM pre-treatment was able to override resistance to CCRT via the STAT3 signaling pathway.

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Section: Introductionmentioning

confidence: 53%

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

et al. 2018

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“…Of these, inhibitor studies have identified the PI3-kinase and the p38 MAPK pathway as being involved in cell survival signaling in cholangiocytes. IL-6 induced PI 3 kinase signaling resulting in activation of Mcl-1 have been reported in several different settings (39,41,49,51). In contrast, the role of p38 MAPK in mediating Mcl-1 expression has not previously been reported to the best of our knowledge.…”

Section: Discussionmentioning

confidence: 88%

“…Mcl-1 is anti-apoptotic and has been implicated as a survival factor for cholangiocarcinoma (35)(36)(37). Moreover, Mcl-1 has been shown to be regulated by IL-6 in a variety of hepatic and other epithelial cancer cell lines such as basal cell carcinoma, gastric cancer and cervical cancer (37)(38)(39)(40)(41). We further assessed the effect of IL-6 on Mcl-1 protein expression in human malignant cholangiocytes.…”

Section: Il-6 Increases Mcl-1 Expressionmentioning

confidence: 99%

Over-expression of interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes

Meng¹,

Yamagiwa²,

Ueno³

et al. 2006

Journal of Hepatology

115

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“…Substantially high microenvironmental IL-6 levels promoted tumor angiogenesis and the development of cervical cancer (Wei et al, 2001a). IL-6 regulated the mcl-1 expression via a PI 3-K/Akt-dependent pathway that might facilitate the oncogenesis of human cervical cancer by modulating the apoptosis threshold (Wei et al, 2001b). It was reported that IL-6 -174G/C polymorphism could affect the transcription rate of a reporter gene in transient transfection studies, which could be associated with the different IL-6 responses to stressful stimuli (Fishman et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Stratification Analysis and Case-control Study of Relationships between Interleukin-6 Gene Polymorphisms and Cervical Cancer Risk in a Chinese Population

Shi¹,

Líu²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mcl-1 through a PI 3-K/Akt pathway

Cited by 153 publications

References 43 publications

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

Over-expression of interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes

Stratification Analysis and Case-control Study of Relationships between Interleukin-6 Gene Polymorphisms and Cervical Cancer Risk in a Chinese Population

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