Livin gene plays a role in drug resistance of colon cancer cells

Wang, Xudong; Xu, Jian; Ju, Shaoqing; Ni, Hongbing; Zhu, Jianhua; Wang, Huimin

doi:10.1016/j.clinbiochem.2010.02.004

Cited by 42 publications

(46 citation statements)

References 24 publications

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“…Therefore, in the present study, we investigated the role of Livin in determining susceptibility to commonly used chemotherapeutic drugs, such as docetaxel, cisplatin and 5-FU, in human HNSCC cell lines. Although several studies have described that Livin contribute to the resistance of various chemotherapeutic drugs including cisplatin in various cancers (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), the present study is the first to demonstrate the correlation between Livin and chemoresistance in human HNSCC.…”

Section: Introductionmentioning

confidence: 81%

Livin enhances chemoresistance in head and neck squamous cell carcinoma

et al. 2017

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Abstract. The responsiveness of head and neck squamous cell carcinoma (HNSCC) to chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer cells is a major cause of chemoresistance. Livin, a member of the human inhibitors of apoptosis protein family, is highly expressed in various human cancer tissues and is associated with tumor progression and poor prognosis in human cancers. The aim of the present study was to evaluate the role of Livin in the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5-fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and PCI50 cells). Reverse transcription polymerase chain reaction and western blotting were performed to determine mRNA and protein expression levels. Cell viability and apoptosis assays were used to assess the functional effects of small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had different sensitivity to chemotherapeutic drugs. Livin knockdown significantly enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells. Livin knockdown induced apoptosis and enhanced chemotherapyinduced apoptosis to cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase compared with that in control cells after cisplatin, 5-FU, or docetaxel treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU and docetaxel. Although further investigations are required to support these findings, our results demonstrated that novel therapeutic strategies with combined use of siRNA targeting Livin and chemotherapeutic agents may have applications in the treatment of advanced HNSCC.

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Section: Introductionmentioning

confidence: 81%

Livin enhances chemoresistance in head and neck squamous cell carcinoma

et al. 2017

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“…Livin-overexpressing cells are more resistant to apoptotic stimuli than are normal cells (Wang et al, 2010;Ding et al, 2013;Li et al, 2013). Thus, Livin intervention contributes to the apoptosis of cancer cells, making Livin an attractive target for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to overexpression analyses, RNAi technology allows a functional analysis by specifically manipulating endogenous livin gene expression directly within Livin-expressing tumor cells (Crnkovic-Mertens et al, 2003. Livin-overexpressing cells are more resistant to apoptotic stimuli than normal cells (Wang et al, 2010;Ding et al, 2013;Li et al, 2013). Thus, Livin intervention contributes to the apoptosis of cancer cells, making it an attractive target for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Effect of RNAi-mediated silencing of Livin gene on biological properties of colon cancer cell line LoVo

Zou¹,

Wang²,

Zhu³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the effect of RNAimediated silencing of the Livin gene on biological properties of the colon cancer cell line LoVo. Interference vectors pSilencer4.1-Ll and pSilencer4.1-L2 targeting the Livin gene were constructed and transfected into LoVo cells. The expression of the Livin gene was determined by RT-PCR and Western blotting. The apoptosis, cell cycle, colony formation, proliferation of LoVo cells, as well as their sensitivity to cisplatin, were detected by flow cytometry, colony formation assay and MTT. Livin mRNA and protein expression in LoVo cells could be effectively silenced by pSilencer4.1-Ll but not pSilencer4.1-L2. In the pSilencer4.1-Ll transfection group, the apoptosis rate of LoVo cells was significantly higher than in the control group (24.2 ± 3.2 vs 8.1 ± 1.4%, P < 0.01), and after 72 h, cell proliferation was clearly decreased (about 70% inhibition). Compared with the control group, the colony formation rate in pSilencer4.1-Ll transfection group was obviously decreased (15 RNAi-mediated Livin gene silencing in LoVo cells ± 4.6 vs 85 ± 5.8%, P < 0.01), with increased proportion of S phase cells (45.7 ± 4.9 vs 28.0 ± 3.0%, P < 0.01), decreased proportion of G1 phase cells (43.0 ± 5.2 vs 62.8 ± 5.1%, P < 0.01), and increased sensitivity to cisplatin (apoptosis rate increased from 43.4 ± 6.9 to 65.3 ± 6.2%, P < 0.01). pSilencer4.1-Ll can effectively silence Livin gene expression in LoVo colon cancer cells, inhibit cell proliferation and colony formation, induce apoptosis, and enhance sensitivity to cisplatin.

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“…Subsequently, it induces DNA damage recognition proteins to signal to downstream effectors such as p53, resulting in cell cycle arrest and apoptosis. To date, little is know on the Livin expression profile in CRC except for preliminary reports [17][18][19][20][21]. Neither is it known about the relationship between Livin expression and cisplatin sensitivity in CRC.…”

Section: Introductionmentioning

confidence: 99%

“…Several reports helped to expand its expression profile to variant tumors such as melanoma, leukemias, bladder, breast, cervical, nasopharyngeal and lung cancer [5][6][7][8]. However, there are only limited reports regarding its expression in CRC except some preliminary studies [17][18][19][20][21]. Previously, Livin expression was described in only 3 colon cancer cell lines (LoVo, Previous reports demonstrated that Livin contributed to resistance to fluorouracil, etoposide, and vincristine for tumor cells, but no studies were intended to explore the relationship between Livin expression and resistance to platinum.…”

mentioning

confidence: 99%

Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells

Ding

Liu

Olsson³

et al. 2012

Tumor Biol.

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The anti-apoptotic factor Livin has been considered critical for tumor progression and poor prognosis for variant types of tumors. But there are only limited reports regarding its expression and biological functions in colon cancer. Here we examined Livin expression in four colon cancer cell lines (HCT116, RKO, KM12C and SW620) in the presence or absence of cisplatin which was used as a model reagent. We found the different response to cisplatin was related to endogenous Livin expression level. From among a panel of apoptosis-related factors (p53, Bcl-2, Bcl-XL, BAX, and survivin), the expression of Livin was up-regulated after cisplatin treatment in a dose-dependent manner. Both the immunocytochemistry and nuclear cytoplasmic fractionation indicated Livin remained in the cytoplasm after treatment with cisplatin. In an attempt to explore the mechanism, we found the elevated expression of Livin was not due to the decreased degradation by proteosome but was enhanced at the mRNA level. Besides, cisplatin treatment activated the mammalian target of rapamycin (mTOR) pathway as shown by increased phosphorylation of Akt1, mTOR, S6K, and 4E-BP1, together with the elevated Livin. The PI3K inhibitor LY294002 inhibited both the phosphorylation of mTOR and up-regulation of Livin. The stable over-expression of Livin inhibited the activation of caspase-3 and led to resistance to cisplatin, while the knock-down of Livin by siRNA rendered colon cancer cells more sensitive to cisplatin. Our study along with others highlighted the potential of Livin for cancer therapy in colon cancer.

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Livin gene plays a role in drug resistance of colon cancer cells

Cited by 42 publications

References 24 publications

Livin enhances chemoresistance in head and neck squamous cell carcinoma

Livin enhances chemoresistance in head and neck squamous cell carcinoma

Effect of RNAi-mediated silencing of Livin gene on biological properties of colon cancer cell line LoVo

Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells

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