Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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Cell Death Induction Mechanism of Non-small Cell Lung Cancer Cell Line, NCI-H1703 by Docetaxel

Docetaxel에 의한 비소세포폐암세포주 NCI-H1703의 세포사멸 유도기전

  • Ha Hyeon-Cheol (Department of Thoracic and Cardiovascular Surgery, Collage of Medicine, Pusan National University) ;
  • Song Seung-Hwan (Department of Thoracic and Cardiovascular Surgery, Collage of Medicine, Pusan National University) ;
  • Park Chin-Su (Department of Thoracic and Cardiovascular Surgery, Collage of Medicine, Pusan National University) ;
  • Kim Jong-Won (Department of Thoracic and Cardiovascular Surgery, Collage of Medicine, Pusan National University) ;
  • Kim Yeong-Dae (Department of Thoracic and Cardiovascular Surgery, Collage of Medicine, Pusan National University)
  • 하현철 (부산대학교 의과대학 흉부외과학교실) ;
  • 송승환 (부산대학교 의과대학 흉부외과학교실) ;
  • 박진수 (부산대학교 의과대학 흉부외과학교실) ;
  • 김종원 (부산대학교 의과대학 흉부외과학교실) ;
  • 김영대 (부산대학교 의과대학 흉부외과학교실)
  • Published : 2006.09.01
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Abstract

Background: Docetaxel has been effectively used as an anti-cancer chemotherapuetic agent for various tumor treatments including lung cancer. However, the cell death induction mechanism(s) involved with docetaxel treatment in lung cancer cells has not been known yet. Material and Method: In the present study, the cellular and biochemical changes of NCI-H1703 cells (non-small cell lung cancer cell line, p53-mutant) after docetaxel treatment have been monitored by flow cytometry, fluorescence microscopy and western blot. Result: Docetaxel treatment significantly resulted in decrease of S phase as well as increase of G2 phase, and consequently evoked an increase of cell death in NCI-H1703 cells. After docetaxel exposure the activations of caspase-3 and caspase-9 were detected. Conclusion: Take together, it is suggested that the docetaxel induces NCI-H1703 cell death by caspase-9 and caspase-3 dependent mitochondrial apoptotic pathway.

Taxene 계 화학요법제로서 항암치료에 사용되고 있는 docetaxel 은 폐암을 포함한 다양한 종양에서 효과적인 항암 치료제로 사용되고 있다. Docetaxel 에 의한 폐암세포의 사멸 유도 기전은 정확히 알려져 있지 않으며, 기전을 연구하기 위해 docetaxel로 처리한 NCI-H1703 세포의 세포주기 및 형태적 변화를 유세포측정기, 형광현미경, western blot 분석법을 통하여 확인하였다. 그 결과 docetaxel 은 의미 있게 S기를 감소시키고 G2기를 증가시킴으로써 NCI-H1703 세포의 사멸을 증가시켰다. Docetaxel에 노출되었을 때 caspase-3와 caspase-9의 활성이 증가되었다. 이들 결과를 종합해볼때, docetaxel 은 H1703 의 세포사멸 유도 시 caspase-3 의존성 미토콘드리아 관련 세포사멸기전으로 apoptosis를 일으키는 것으로 생각한다.

Keywords

References

  1. Langer CJ. Advanced non-small cell lung carcinoma: the emerging role of docetaxel. Invest New Drugs 2000;18: 17-28 https://doi.org/10.1023/A:1006313927411
  2. Calderoni A, Cerny T. Taxanes in lung cancer. A review with focus on the European experience. Crit Rev Oncol Hematol 2001;38:105-27 https://doi.org/10.1016/S1040-8428(00)00121-9
  3. Herbst RS, Khuri FR. Mode of action of docetaxel - a basis for combination with novel anticancer agents. Cancer Treat Rev 2003;29:407-15 https://doi.org/10.1016/S0305-7372(03)00097-5
  4. Ganansia-Leymarie V, Bischoff P, Bergerat JP, Holl V. Signal transduction pathways of taxanes-induced apoptosis. Curr Med Chem Anti-Canc Agents 2003;3:291-306 https://doi.org/10.2174/1568011033482422
  5. King TC, Akerley W, Fan AC, et al. p53 mutations do not predict response to paclitaxel in metastatic nonsmall cell lung carcinoma. Cancer 2000;89:769-73 https://doi.org/10.1002/1097-0142(20000701)89:1<53::AID-CNCR8>3.0.CO;2-6
  6. Kolfschoten GM, Hulscher TM, Duyndam MC, Pinedo HM, Boven E. Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and apoptotic morphology in unselected human ovarian cancer cell lines as a response to docetaxel. Biochem Pharmacol 2002;63:733-43 https://doi.org/10.1016/S0006-2952(01)00895-4
  7. Yoon SJ, Lee H, Shin Y, Kim YI, Kim CY, Chang H. Estimation of the burden of major cancers in Korea. J Korean Med Sci 2002;17:604-10 https://doi.org/10.3346/jkms.2002.17.5.604
  8. Cullen M. Lung cancer. 4: chemotherapy for non-small cell lung cancer: the end of the beginning. Thorax 2003;58: 352-6 https://doi.org/10.1136/thorax.58.4.352
  9. Ferreira CG, Tolis C, Span SW, et al. Drug-induced apoptosis in lung cnacer cells is not mediated by the Fas/FasL (CD95/APO1) signaling pathway. Clin Cancer Res 2000;6: 203-12
  10. Zelivianski S, Spellman M, Kellerman M, et al. ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. Int J Cancer 2003;107:478-85 https://doi.org/10.1002/ijc.11413
  11. Masuda A, Maeno K, Nakagawa T, Saito H, Takahashi T. Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by antimicrotubule agents in human lung cancers. Am J Pathol 2003;163:1109-16 https://doi.org/10.1016/S0002-9440(10)63470-0
  12. Chang JC, Wooten EC, Tsimelzon A, et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet 2003;362: 362-9 https://doi.org/10.1016/S0140-6736(03)14023-8
  13. Georgoulias V. Docetaxel (taxotere) in the treatment of nonsmall cell lung cancer. Curr Med Chem 2002;9:869-77 https://doi.org/10.2174/0929867024606812
  14. Wang H. Combined effect of docetaxel and cisplatin for nonsmall cell lung cancer cell lines in vitro. Nagoya J Med Sci 2000;63:129-37
  15. Morris SM. A role for p53 in the frequency and mechanism of mutation. Mutat Res 2002;511:45-62 https://doi.org/10.1016/S1383-5742(01)00075-8
  16. Illidge TM, Cragg MS, Fringes B, Olive P, Erenpreisa JA. Polyploid giant cells provide a survival mechanism for p53 mutant cells after DNA damage. Cell Biol Int 2000;24: 621-33 https://doi.org/10.1006/cbir.2000.0557
  17. Weigel TL, Lotze MT, Kim PK, Amoscato AA, Luketich JD, Odoux C. Paclitaxel-induced apoptosis in non-small cell lung cancer cell lines is associated with increased caspase-3 activity. J Thorac Cardiovasc Surg 2000;119:795-803 https://doi.org/10.1016/S0022-5223(00)70016-X
  18. Huisman C, Ferreira CG, Broker LE, et al. Paclitaxel triggers cell death primarily via caspase-independent routes in the non-small cell lung cancer cell line NCL-H460. Clin Cancer Res 2002;8:596