Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma

Wang, Zhichao; Liu, Long-Zi; Liu, Xin-Yang; Hu, Jun; Wu, Yingjie; Shi, Jing; Long, Yang; Duan, Meng; Wang, Xiaoying; Zhou, Jian; Fan, Jia; Gao, Qiang

doi:10.1007/s13277-015-3407-1

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…Previous study indicated that pretreatment with PPI significantly enhanced the sensitivity of tumors [13]. Consistently, the present study indicated that PPI pantoprazole arrested the MDR leukemic K562/A02 and K562/ADM cells in S phase and The classical mechanism of MDR is related with MDR1 gene and its production P-gp [14][15][16]. As a glycoprotein with 1280 amino acids, P-gp can bind hydrophobic antitumor drugs through the hydrophobic cites and pump drugs out of cells against the concentration gradient with energy provided by ATP to decrease the intracellular drug concentration and result in resistance.…”

Section: Discussionsupporting

confidence: 88%

Pantoprazole Induces Apoptosis of Leukemic Cells by Inhibiting Expression of P-Glycoprotein/Multidrug Resistance-Associated Protein-1 Through PI3K/AKT/mTOR Signaling

Miao

Tang

Jiang

2017

Indian J Hematol Blood Transfus

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This study aims to investigate the effects and mechanism of pantoprazole on multidrug resistant leukemia K562/A02 and K562/ADM cell lines. K562/A02 and K562/ADM cells at logarithmic growth phase were pre-treated with different concentration of pantoprazole (0, 50, 100, 200 μg/mL) for 24 h. Flow cytometry was used to measure the cell growth cycle and apoptosis. RT-PCR and Western blot were used to measure the expression of p-PI3K, p-AKT, p-mTOR, P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1). Pantoprazole pretreatment significantly increased the ratio of G0/G1 phase but decreased the S phase of K562/A02 and K562/ADM cells in dose-dependent manner ( < 0.05). Flow cytometry analysis indicated that pretreatment of leukemic cells with pantoprazole induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analysis indicated that pantoprazole pretreatment inhibited the mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, P-gp and MRP1 in K562/A02 and K562/ADM cells in a dose-dependent manner ( < 0.05). Pantoprazole arrested cell cycle and induced apoptosis of multidrug resistant leukemic cells by inhibiting the expression of P-gp and MRP1 through PI3K/Akt/mTOR signaling pathway.

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Section: Discussionsupporting

confidence: 88%

Pantoprazole Induces Apoptosis of Leukemic Cells by Inhibiting Expression of P-Glycoprotein/Multidrug Resistance-Associated Protein-1 Through PI3K/AKT/mTOR Signaling

Miao

Tang

Jiang

2017

Indian J Hematol Blood Transfus

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“…Several studies, performed in Asian populations, have investigated associations between ABCB1 polymorphisms (including rs1128503) and the risk of developing HCC. A recent meta-analysis[ 55 ] showed that polymorphic alleles of the ABCB1 gene significantly increased HCC risk. In analyses of subgroups with different types of variations, both synonymous and non-synonymous polymorphisms were associated with elevated liver cancer susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Genetic biomarkers for hepatocellular cancer risk in a caucasian population

Mattia

Cecchin

Polesel

et al. 2017

WJG

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AIMTo uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma (HCC) susceptibility in Caucasians.METHODSThe present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two, independent, HCC-free, age/sex-matched control groups. The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation. The first control group comprised 167 patients that were matched to the HCC cohort for the percentage of hepatitis B (HBV) and/or hepatitis C (HCV) infections. A second control group included 192 virus-free, healthy individuals that were used to evaluate the generalizability of the identified predictive markers. All cases and controls were Caucasian. The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways. The study end-point was to assess the association between genetic variants and HCC onset.RESULTSFive genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV. According to a dominant model, reduced HCC risk was associated with three polymorphisms: ERCC1 rs3212986 (OR = 0.46, 95%CI: 0.30-0.71, P = 0.0005), GST-P1 rs1138272 (OR = 0.41, 95%CI: 0.21-0.81, P = 0.0097), and CYP17A1 rs743572 (OR = 0.50, 95%CI: 0.31-0.79, P = 0.0032). Conversely, according to a recessive model, increased HCC risk was associated with two polymorphisms: XRCC3 rs1799794 (OR = 3.70, 95%CI: 1.02-13.39, P = 0.0461) and ABCB1 rs1128503 (OR = 2.06, 95%CI: 1.18-3.61, P = 0.0111). These associations remained significant in a subgroup analysis, where patients were stratified according to viral status (HBV- or HCV-positive serology). Two variants exhibited a serology-specific effect: ABCB1 rs1128503 (OR = 4.18, 95%CI: 1.55-11.29, P = 0.0048) showed an effect in the HBV-positive subgroup; and ERCC1 rs3212986 (OR = 0.33, 95%CI: 0.18-0.60, P = 0.0003) showed an effect in the HCV-positive subgroup. Among the five markers identified, ERCC1 rs3212986 (OR = 0.43, P < 0.0001) and CYP17A1 rs743572 (OR = 0.73, P = 0.0310) had a different distribution in patients with HCC compared to healthy individuals. With a recursive partitioning approach, we also demonstrated that significant gene-gene interactions between ERCC1 rs3212986, CYP17A1 rs743572, GST-P1 rs1138272, and the previously described UGT1A7*3 predictive marker, played a role in the complex trait of HCC susceptibility.CONCLUSIONWe identified five polymorphisms and interactions that contributed crucially to predicting HCC risk. These findings represented an important step towards improving HCC diagnosis and management.

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“…TSCC is the most common type of oral squamous cell carcinoma, with strong invasiveness, easy occurrence of neck lymphatic metastasis and poor outcomes . The quality of life in TSCC patients is often reduced by dysphasia, as well as difficulties in chewing and swallowing.…”

Section: Discussionmentioning

confidence: 99%

The HSP90/Akt pathway may mediate artemether‐induced apoptosis of Cal27 cells

Wang

et al. 2019

FEBS Open Bio

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Tongue squamous cell carcinoma is the most common malignant tumor in oral and maxillofacial regions. Recent research has found that artemether can inhibit growth and induce apoptosis of cancer cells, although the mechanism is not clear. The present study aimed to explore the correlation between the HSP90/Akt pathway and artemether‐induced apoptosis of Cal27 cells. A cell counting kit‐8 and flow cytometry were used to detect the proliferation and apoptosis of Cal27 cells, respectively, mRNA expression was examined by quantitative RT‐PCR, and protein expression was detected by western blotting. Our data revealed that artemether can inhibit growth and induce apoptosis of Cal27 cells. As the artemether concentration was increased, we observed downregulation of the expression of HSP90, p‐Akt and p‐mTOR in Cal27 cells, whereas the expression of Akt was not significantly changed. We also observed a time‐dependent decrease in the expression of HSP90, p‐Akt and p‐mTOR during exposure to 0.1 mg·mL−1 artemether. In conclusion, the HSP90/Akt pathway may be involved in artemether‐induced apoptosis of Cal27 cells.

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Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma

Cited by 9 publications

References 44 publications

Pantoprazole Induces Apoptosis of Leukemic Cells by Inhibiting Expression of P-Glycoprotein/Multidrug Resistance-Associated Protein-1 Through PI3K/AKT/mTOR Signaling

Pantoprazole Induces Apoptosis of Leukemic Cells by Inhibiting Expression of P-Glycoprotein/Multidrug Resistance-Associated Protein-1 Through PI3K/AKT/mTOR Signaling

Genetic biomarkers for hepatocellular cancer risk in a caucasian population

The HSP90/Akt pathway may mediate artemether‐induced apoptosis of Cal27 cells

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