Down-regulation of ALKBH2 increases cisplatin sensitivity in H1299 lung cancer cells

Wu, Shuangshuang; Xu, Wei; Liu, Shan; Chen, Bo; Wang, Xueli; Wang, Yan; Liu, Shifeng; Wu, Jianzhong

doi:10.1038/aps.2010.216

Cited by 36 publications

(31 citation statements)

References 26 publications

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“…In other ALKBHs, ALKBH8 contributes to progression of human bladder cancer (12). The other homolog, ALKBH2, downregulation of it increases cisplatin sensitivity in human lung cancer cell line (40). By sharp contrast, the antitumor activity of ALKBH2 has been reported in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

PCA-1/ALKBH3 Contributes to Pancreatic Cancer by Supporting Apoptotic Resistance and Angiogenesis

et al. 2012

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The PCA-1/ALKBH3 gene implicated in DNA repair is expressed in several human malignancies but its precise contributions to cancer remain mainly unknown. In this study, we have determined its functions and clinical importance in pancreatic cancer. PCA-1/ALKBH3 functions in proliferation, apoptosis and angiogenesis were evaluated in human pancreatic cancer cells in vitro and in vivo. Further, PCA-1/ALKBH3 expression in 116 patients with pancreatic cancer was evaluated by immunohistochemistry. siRNA-mediated silencing of PCA-1/ALKBH3 expression induced apoptosis and suppressed cell proliferation. Conversely, overexpression of PCA-1/ALKBH3 increased anchorage-independent growth and invasiveness. In addition, PCA-1/ALKBH3 silencing downregulated VEGF expression and inhibited angiogenesis in vivo. Furthermore, immunohistochemical analysis showed that PCA-1/ALKBH3 expression was abundant in pancreatic cancer tissues, where it correlated with advanced tumor status, pathological stage and VEGF intensity. Importantly, patients with low positivity of PCA-1/ALKBH3 expression had improved postoperative prognosis compared with those with high positivity. Our results establish PCA-1/ALKBH3 as important gene in pancreatic cancer with potential utility as a therapeutic target in this fatal disease. Cancer Res; 72(18); 4829-39. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

PCA-1/ALKBH3 Contributes to Pancreatic Cancer by Supporting Apoptotic Resistance and Angiogenesis

et al. 2012

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“…To date, 8 human homologues of the Escherichia coli DNA repair enzyme ALKB ( ALKBH1-8 ) have been identified, which are involved in repair of alkylation damage in DNA and RNA (22). Among them, ALKBH3 was reported to be significantly overexpressed in lung adenocarcinoma cells and contributes to NSCLC cell survival (23), although combined treatment modalities with cisplatin- and lentivirus-mediated ALKBH2 downregulation were significantly more potent in inhibiting lung cell growth and inducing apoptosis than monochemotherapy (24). However, little is known for the role of ALKBH1 in NSCLC survival and/or therapy response.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

Zhao

et al. 2012

Clinical Cancer Research

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Purpose Genetic variation may influence chemotherapy response and overall survival in cancer patients. Experimental design We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA). Results Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population. Conclusion In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients.

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“…In a study of brain tumor samples taken from patients treated with alkylating drugs such as temozolomide (TMZ), all samples contained elevated levels of ALKBH2 mRNA over those from patients receiving radiotherapy . TMZ resistance in several glioblastoma cell lines as well as cisplatin resistance in H1299 lung cancer cells was suppressed by siRNA‐mediated knockdown of ALKBH2, and reduced ALKBH2 activity improves sensitivity to alkylating drugs . These findings have stimulated recent efforts to find inhibitors of ALKBH2 …”

Section: Figurementioning

confidence: 99%

Fluorescence Probes for ALKBH2 Allow the Measurement of DNA Alkylation Repair and Drug Resistance Responses

Wilson

Beharry

Srivastava³

et al. 2018

Angewandte Chemie

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The DNA repair enzyme ALKBH2 is implicated in both tumorigenesis as well as resistance to chemotherapy in certain cancers. It is currently under study as a potential diagnostic marker and has been proposed as a therapeutic target. To date, however, there exist no direct methods for measuring the repair activity of ALKBH2 in vitro or in biological samples. Herein, we report a highly specific, fluorogenic probe design based on an oligonucleotide scaffold that reports directly on ALKBH2 activity both in vitro and in cell lysates. Importantly, the probe enables the monitoring of cellular regulation of ALKBH2 activity in response to treatment with the chemotherapy drug temozolomide through a simple fluorescence assay, which has only previously been observed through indirect means such as qPCR and western blots. Furthermore, the probe provides a viable high‐throughput assay for drug discovery.

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Down-regulation of ALKBH2 increases cisplatin sensitivity in H1299 lung cancer cells

Cited by 36 publications

References 26 publications

PCA-1/ALKBH3 Contributes to Pancreatic Cancer by Supporting Apoptotic Resistance and Angiogenesis

PCA-1/ALKBH3 Contributes to Pancreatic Cancer by Supporting Apoptotic Resistance and Angiogenesis

Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

Fluorescence Probes for ALKBH2 Allow the Measurement of DNA Alkylation Repair and Drug Resistance Responses

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