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Effects of arsenic trioxide on human renal cell carcinoma lines in vitro

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Abstract

Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms.Methods: The microculture tetrazolium (MTT) assay was used to determine the anti-proliterative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc.Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4. 0 μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells, but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen.Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

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References

  1. Wang ZY. Arsenic compounds as anticancer agents. Cancer Chemother Pharmacol 2001; 48 (suppl): 572–576.

    Article  Google Scholar 

  2. Wan YX, Ma JH, Chen YX, et al. Establishment and biological characteristics of six human renal carcinoma cell lines. Chin J Urol 2002;23(9): 521–523.

    Google Scholar 

  3. Shen ZX, Chen GQ, Ni JH, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997;89: 3354–3360.

    PubMed  CAS  Google Scholar 

  4. Shen ZY, Tan LJ, Cai WJ, et al. Arsenic trioxide-mediated cytotoxicity and apoptosis of esophageal carcinoma in vitro. Int J Mol Med 1999;4: 33–37.

    PubMed  CAS  Google Scholar 

  5. Shi YH, Tan LJ, Li H, et al. Study on arsenic trioxide induced apoptosis in tumor cell lines of digestive tract. Acta Univ Med Sec Shanghai 1999;19: 242–244.

    CAS  Google Scholar 

  6. Akao Y, Nakagawa Y, Akiyama K. Arsenic trioxide induces apoptosis in neuroblastma cell lines through the activation of caspase-3 in vitro. FEBS Lett 1999; 455: 459.

    Article  Google Scholar 

  7. Seol JG, Park WH, Kim ES, et al. Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-I head and neck cancer cells. Int J Oncol 2001; 18 (2): 249–225.

    PubMed  CAS  Google Scholar 

  8. Maeda H, Hori S, Nishitoh H, et al. Tumor growth inhibition by arsenic trioxide (As2O3) in the orhtotopic metastasis model of androgen-independent prostate cancer. Cancer Res 2001; 61: 5432–5440.

    PubMed  CAS  Google Scholar 

  9. Uslu R, Sanli UA, Sezgin C, et al. Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines. Clin Cancer Res 2000; 6: 4957–4964.

    PubMed  CAS  Google Scholar 

  10. Baj G, Arnulfo A, Deaglio S, et al. Arsenic trioxide and breast cancer: analysis of the apoptotic, differentiative and immunomodulatory effects. Breast Cancer Res Treat 2002;73: 61–73.

    Article  PubMed  CAS  Google Scholar 

  11. Xiao DM, Sun GL, Su H et al. Effects of As2O3 on the BCR/ABL protein tyrosine phosphorylation in K562 Cell. Chin J Hematol 1999;20(12): 637–639.

    CAS  Google Scholar 

  12. Park JW, Choi YJ, Jang MA, et al. Arsenic trioxide induces G2/M growth arrest and apoptosis after caspase-3 activation and bcl-2 phosphorylation in promonocytic U937 cells. Biochem Biophys Res Commun 2001; 286 (4): 726–734.

    Article  PubMed  CAS  Google Scholar 

  13. Park WH, Seol JG, Kim ES, et al. Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res 2000, 60(11): 3065–3071.

    PubMed  CAS  Google Scholar 

  14. Lin C, Deng YP, Zheng J et al. Arsenic trioxide induces human tumor cell apoptosis and G2 + M arrest whereas cancers HPV16 DNA immortalized cervical epithelial cells G1 block. Acta Acad Med Sinica 2000; 22 (2): 124–129.

    Google Scholar 

  15. Liu L, Qin S, Chen H, et al. An Experimental study on arsenic trioxide-selectively induced human hepatocarcinoma cell lines apoptosis and its related genes. Chin J Hepatopathy 2000;8(6): 267–369.

    CAS  Google Scholar 

  16. Gu QL, Li NL, Lin YZ, et al. An experiment on arsenic trioxide inducing differentiation of gastric cancer cell lines. Tumor 2000;20(6): 410–412.

    Google Scholar 

  17. Du YH, Ho PC. Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines. Cancer Chemother Pharmacol 2001;47(6): 481–490.

    Article  PubMed  CAS  Google Scholar 

  18. Pu YS, Hour TC, Chen J, et al. Cytotoxicity of arsenic trioxide to transitional carcinoma cells. Urology 2002; 60 (2): 346–350.

    Article  PubMed  Google Scholar 

  19. Dai J, Weinberg RS, Waxman S et al. Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system. Blood 1999;93(1): 268–277.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Coordinating Group of Biologic Therapy, Cancer Hospital, Chinese Academy of Medical Sciences, 100021, Beijing

    Qu Feng-lian, Li Yan-fen, Wan Yun-xia, Ma Jian-hui, Shi Wei, Chu Da-tong & Sun Yan

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  1. Qu Feng-lian
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  2. Li Yan-fen
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  3. Wan Yun-xia
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  4. Ma Jian-hui
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  5. Shi Wei
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  6. Chu Da-tong
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  7. Sun Yan
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Feng-lian, Q., Yan-fen, L., Yun-xia, W. et al. Effects of arsenic trioxide on human renal cell carcinoma lines in vitro. Chin. J. Integr. Med. 10, 48–51 (2004). https://doi.org/10.1007/BF02836561

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