Chengfang Xu

Sun Yat-Sen University of Medical Sciences, Shengcheng, Guangdong, China

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Publications (7)18.02 Total impact

  • Journal of Biophotonics 03/2015; 9999(9999). DOI:10.1002/jbio.201400131 · 3.86 Impact Factor
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    ABSTRACT: Some of lipophilic statins have been reported to enhance toxicities induced by antineoplastic agents but the underling mechanism is unclear. The authors investigated the involvement of Cx43-mediated gap junction intercellular communication (GJIC) in the effect of simvastatin on the cellular toxicity induced by etoposide in this study. The results showed that a major component of the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce cytotoxicity enhances etoposide toxicity by increasing gap junction coupling. The augmentative effect of simvastatin on GJIC was related to the inhibition of PKC-mediated Cx43 phosphorylation at ser368 and subsequent enhancement of Cx43 membrane location induced by the agent. The present study suggests the possibility that upregulation of gap junctions may be utilized to increase the efficacy of anticancer chemotherapies.
    Toxicology 08/2013; DOI:10.1016/j.tox.2013.08.013 · 3.75 Impact Factor
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    ABSTRACT: In recent years, it has been reported that CHFR may be a useful biomarker for chemotherapeutic response to microtubule inhibitors in some tumor cells. The purpose of the present study was to test the hypothesis and to elucidate the underlying mechanism in endometrial cancer cells. First, we effectively inhibited CHFR expression at both the mRNA and protein levels using siRNA targeting the CHFR gene in Ishikawa and Hec-1a cells. We found that inhibition of CHFR expression significantly enhanced the cytotoxicity of taxol to both cell types, which was confirmed again by colony formation assays. Moreover, suppression of CHFR induced a significant increase of the mitotic index and much lower numbers of cells at the G2/M phase in both cells treated with taxol, indicating mitotic checkpoint impairment. On the other hand, the number of apoptotic cells significantly increased in Ishikawa and Hec-1a cells transfected with CHFR siRNA after treatment with taxol, which was associated with cyclin B1 nuclear localization. Our data indicate that RNA interference targeting CHFR can sensitize endometrial cancer cells to taxol and CHFR may be a promising molecular target to enhance the therapeutic effect of taxol for endometrial cancer.
    Oncology Reports 04/2012; 28(1):248-54. DOI:10.3892/or.2012.1752 · 2.19 Impact Factor
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    ABSTRACT: Loss or mutation of the PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene is associated with resistance to epidermal growth factor receptor (EGFR) inhibitors. However, the mechanism underlying remains elusive. In this study, we aimed to explore whether sensitivity to the EGFR tyrosine kinase inhibitor (TKI) is affected by PTEN status in endometrial cancer cells. PTEN siRNA and the PTEN gene were transfected into HEC-1A and Ishikawa endometrial cancer cells using lentiviral vectors. Cells were treated under various concentrations of RG14620 and rapamycin, which are EGFR and mammalian target of rapamycin (mTOR) inhibitors, respectively. The IC(50) of RG16420 was determined by using the MTT method. Cell apoptosis and the cell cycle were studied, and activation of EGFR, AKT, and p70S6 were detected by Western blot analysis. Loss of PTEN promoted cell proliferation and led to significant increases in the levels of EGFR, phospho-EGFR, AKT, phospho-AKT, and phospho-mTOR proteins. Ishikawa and HEC-1A(PTENkd) cells that displayed loss and inactivation of PTEN function were resistant to RG14620. HEC-1A and Ishikawa(PTEN) cells with intact PTEN were sensitive to RG14620. The combination of two inhibitors was more effective than both monotherapies, particularly in carcinoma cells with PTEN dysfunction. Decreased phospho-EGFR protein expression was observed in all cell lines that were sensitive to RG14620. Decreased phospho-AKT and phospho-p70S6 protein expression was observed in PTEN-intact cells that were sensitive to RG14620. PTEN loss results in resistance to EGFR TKI, which was reversed by PTEN reintroduction or mTOR inhibitor treatment. The combined treatment of EGFR TKI and the mTOR inhibitor provided a synergistic effect by promoting cell death in PTEN-deficient and PTEN-intact endometrial cancer cells, particularly in PTEN-deficient carcinoma cells with up-regulated EGFR activation.
    Molecular and Cellular Biochemistry 09/2011; 361(1-2):19-29. DOI:10.1007/s11010-011-1082-0 · 2.39 Impact Factor
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    ABSTRACT: Impairment of a cell cycle checkpoint is often associated with sensitivity to chemotherapeutic drugs. Here, we studied the correlations between the checkpoint with forkhead-associated and ring finger (CHFR) gene expression and responses to paclitaxel in endometrial cancer cells. We cultured 6 endometrial cancer cell lines exposed to paclitaxel, studied the cell cytotoxicity, cell cycle distribution, CHFR expression, and methylation status before and after a demethylation agent (5-aza) treatment. CHFR was silenced by small interfering RNA (siRNA). Then we examined tumor growth and CHFR expression with paclitaxel alone or combined with 5-aza pretreatment in vivo. We found that HEC-1B, RL-952, and AN3CA cells were sensitive to paclitaxel. Moreover, CHFR was weakly expressed in these cells, whereas paclitaxel-resistant cells (ISH, HEC-1A, and KLE) had high CHFR expression. Then we found that restored expression of CHFR by demethylation decreased the sensitivity to paclitaxel in AN3CA cells. In addition, cells with CHFR demethylation resulted in G2/M phase arrest that induced to paclitaxel resistance. These results were confirmed again in small interfering RNA-transfected HEC-1A cells. Furthermore, in nude mice model, restored expression of CHFR by demethylation inhibited tumor growth and decreased sensitivity to paclitaxel. Our data suggest that CHFR suppression regulated by hypermethylation may sensitize endometrial cancer cells to paclitaxel, and CHFR may be a promising marker to predict the response of endometrial cancer to paclitaxel.
    International Journal of Gynecological Cancer 08/2011; 21(6):996-1003. DOI:10.1097/IGC.0b013e31821e05e8 · 1.95 Impact Factor
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    ABSTRACT: The type-1 insulin-like growth factor receptor (IGF-1R) is over-expressed by endometrial carcinoma, level of IGF-1R has been correlated with tumor progression, and high IGF-1R expression has been found to be an important prognostic factor. In the study, we used lentivirus-mediated shRNA targeting IGF-1R to silence its expression, then assessed the effect of down-regulation of this receptor on cell growth and chemosensitivity to cisplatin. Lentivirus-mediate shRNA was designed and transfected to the endometrial carcinoma HEC-1B cell. The IGF-1R mRNA and related protein expression, cell proliferation ability, cell apoptosis, and cell cycle change were detected. Cell proliferation inhibition rates, cell apoptosis, and level of cleaved caspase-9 were measured in various concentrations of cisplatin. The mRNA and protein level of IGF-1R, and the phosphorylated protein p-Akt, p-Erk were all suppressed after transfection. Cell proliferation was inhibited in successive five days after transfection, the highest inhibition rate was 43.28 ± 3.55% on day 5. After transfection, 24.96 ± 1.05% cells were in G(2)/M phase, and cell apoptotic rate increased from 10.66 ± 0.08 to 19.92 ± 1.34%. In various concentrations of cisplatin, transfected cells proliferation was significantly inhibited which made the IC50 value drop from 21.85 uM to 10.58 uM. Incubation with different concentrations of cisplatin for 48 h, cells apoptotic rate increased to 41.92 ± 2.5, 31.13 ± 2.76, 22.21 ± 4.63%, respectively, which was accompanied with increased cleaved caspase-9 expression. Lentivirus-mediated shRNA targeting IGF-1R has the potential to develop as a clinical treatment method in advanced and chemoresistant endometrial carcinoma.
    Molecular and Cellular Biochemistry 03/2011; 353(1-2):225-33. DOI:10.1007/s11010-011-0790-9 · 2.39 Impact Factor
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    ABSTRACT: This study was conducted to evaluate and compare molecular and cellular effects of paclitaxel in combination with epidermoid growth factor receptor (EGFR) or/and mammalian target of rapamycin( mTOR) inhibitors with two endometrial cancer lines HEC-1A and Ishikawa. Treatment was with the EGFR inhibitor RG14620, the mTOR inhibitor rapamycin, and the conventional cytotoxic drug paclitaxel, alone or in combination. The 50% inhibitory concentration (IC50) and cell viability were determined by the MTT assay. Multiple drug effect/ combination indexes (CI) analysis was applied to assess interactions between paclitaxel and the two inhibitors. Apoptosis and cell cycling were evaluated by flow cytometry analysis. Western blotting was performed to evaluate the related protein alteration in PI3K/AKT signaling pathway. RG14620, rapamycin and paclitaxel showed obvious dose-dependent growth inhibition with time. The IC50 of paclitaxel at 24 hours decreased significantly when pretreated with low doses of RG14620 and Rapamycin alone or in combination. Moreover, combination index (CI) of paclitaxel with each inhibitor was larger than 1, indicating a synergistic effect between pairs of drugs in these two cell lines. FACS analysis showed the cell apoptosis rate increased with a synergistic effect. On Western blotting, activation of PI3K/AKT pathway was detected in both two cell lines in the control case. When paclitaxel was used as a single-agent or in combinations, the protein expression of PI3K/AKT pathway totally abated, especially in HEC-1A cells, suggesting a role in chemoresistance. The combination of three drugs induced the greatest over-expression of caspase-3. Combining targeted inhibitors with cytotoxic chemotherapy appears to be a promising strategy for the effective treatment of endometrial cancer which merits further clinical investigation.
    Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(11):2951-7. · 1.50 Impact Factor

Publication Stats

25 Citations
18.02 Total Impact Points

Institutions

  • 2015
    • Sun Yat-Sen University of Medical Sciences
      Shengcheng, Guangdong, China
  • 2011–2013
    • Sun Yat-Sen University
      • Department of Gynecology
      Shengcheng, Guangdong, China