Proteomics-based identification of secreted protein dihydrodiol dehydrogenase 2 as a potential biomarker for predicting cisplatin efficacy in advanced NSCLC patients

Kuang, Peng; Zhou, Caicun; Li, Xuefei; Ren, Shengxiang; Li, Bing; Wang, Yongsheng; Li, Jiayu; Tang, Liang; Zhang, Jie; Zhao, Yiqing

doi:10.1016/j.lungcan.2012.03.016

Cited by 12 publications

(10 citation statements)

References 35 publications

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“… 9 AKR1C2 could serve as a biomarker to evaluate the efficacy of chemotherapy in patients with advanced non-SCLC. 10 AKR1C4 is one of the susceptible genes for common familial colorectal cancer. 11 AKR1C1 is a less well-known member of the AKR1C family, and was reported to be highly expressed in different cancer types such as prostate cancer, 12 endometrial cancer, 13 and non-SCLC.…”

Section: Introductionmentioning

confidence: 99%

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells

Tian¹,

Li²,

Jiang³

et al. 2016

LCTT

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AKR1C1 is a member of the AKR1C family, which not only plays an important role in hormone metabolism but is believed to be involved in carcinogen metabolism. Our previous study demonstrated that AKR1C1 was highly expressed in lung tumor tissues as compared with the tumor-adjacent tissues. Small-cell lung cancer (SCLC) is a special type of lung cancer. Surgical treatment of SCLC is usually difficult due to the high degree of malignancy and early metastasis, and difficulty in obtaining clinical specimens. There is not much basic or clinical research on SCLC in the People’s Republic of China even in recent years. To investigate the mechanism of AKR1C1 in the pathogenesis of SCLC, the present study used H446 cell line to see whether AKR1C1 could affect the proliferation or migration of SCLC cells, and used a lentivirus to build the AKR1C1 overexpression and under-expression cell lines. The results indicated that AKR1C1 was an important inducement in the proliferation and migration of H446 cells. AKR1C1 promoted cell proliferation and played a vital role in the migration of SCLC cells. These results were also verified in nude mice in vivo. In conclusion, AKR1C1 plays an important role in the development and progression of SCLC and may represent an independent biomarker for assessment of the primary prognosis and therapy of SCLC.

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Section: Introductionmentioning

confidence: 99%

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells

Tian¹,

Li²,

Jiang³

et al. 2016

LCTT

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“…[NSCLC] and small-cell lung cancer) remains the leading cause of cancer-related deaths in the world. 1 Although great efforts have been made toward improving early diagnosis and effective treatment, including findings of new biomarkers, [2][3][4] establishment of modified operation, and development of specific drugs, [5][6][7][8][9] the prognosis is still poor.…”

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confidence: 99%

WT1 Promotes Invasion of NSCLC via Suppression of CDH1

Zhu

Qian

et al. 2013

Journal of Thoracic Oncology

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“…Acquired cisplatin resistance is the major cause of chemotherapy failure in the treatment of lung cancer; thus, we speculated that dual inhibition of APE1 and autophagic flux would overcome cisplatin resistance. We tested the effects on cell proliferation and apoptosis in acquired cisplatin-resistant A549 cells (parental A549 cells were exposed to cisplatin to develop the acquired resistant cell line, named A549/CDDP [ 32 ]) following dual inhibition of both the APE1 and autophagy. The cell viability was decreased in A549/CDDP cells receiving combinatorial treatment with cisplatin and CQ or cisplatin and APE1 siRNA compared with the vehicle or mono-treatment (Fig.…”

Section: Resultsmentioning

confidence: 99%

Proteomics reveals a therapeutic vulnerability via the combined blockade of APE1 and autophagy in lung cancer A549 cells

et al. 2020

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Background Drug resistance is a major cause of therapeutic failure that is often associated with elevated autophagy and apurinic/apyrimidinic endonuclease 1 (APE1) expression. Herein, we investigated the role of APE1 and autophagy in A549 cells treated with cisplatin. Methods SILAC proteomics was applied to obtain a panoramic view of cisplatin treatment in KRAS G12S -mutant A549 cells. Quantity analysis of cellular apoptosis and autophagy was based on flow cytometry. Western blotting was used to examine the expression levels of apoptosis- and autophagy-related proteins, as well as those of APE1. Knockdown of APE1 was achieved by RNA interference. Immunoprecipitation was further employed to reveal the molecular interaction of APE1, p53, and LC3 when A549 cells were exposed to cisplatin. Results SILAC proteomics revealed that 72 canonical pathways, including base excision repair (BER) and autophagy signalling pathways, were regulated after cisplatin treatment in A549 cells. Cisplatin markedly induced autophagy and apoptosis in A549 cells, accompanied by remarkable APE1 increase. Suppression of autophagy enhanced the inhibition effect of cisplatin on cell growth, proliferation, and colony formation; however, APE1 inhibition enhanced the expression of LC3-I/II, suggesting that APE1 and autophagy are compensatory for cell survival to evade the anticancer action of cisplatin. Immunoprecipitation results revealed the triple complex of APE1-p53-LC3 in response to cisplatin plus CQ in A549 cells. Dual inhibition of APE1 and autophagy significantly enhanced cisplatin-induced apoptosis, which eventually overcame drug resistance in cisplatin-resistant A549 cells. Conclusions Dual inhibition of APE1 and autophagy greatly enhances apoptosis in parental KRAS G12S -mutant A549 cells and cisplatin-resistant A549 cells via regulation of APE1-p53-LC3 complex assembly, providing therapeutic vulnerability to overcome cisplatin resistance in the context of KRAS G12S -mutant lung cancer.

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Proteomics-based identification of secreted protein dihydrodiol dehydrogenase 2 as a potential biomarker for predicting cisplatin efficacy in advanced NSCLC patients

Cited by 12 publications

References 35 publications

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells

WT1 Promotes Invasion of NSCLC via Suppression of CDH1

Proteomics reveals a therapeutic vulnerability via the combined blockade of APE1 and autophagy in lung cancer A549 cells

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