- 1. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
- 2. Chest Oncology Institute, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
Apoptosis is an important means to regulate cell proliferation and maintain homeostasis. Recent researches have shown that the B-cell lymphoma-2 (BCL-2) family not only plays a dominant role in the regulation of normal cell apoptosis, but also plays a crucial role in the formation of tumor genesis, progression and subsequent drug resistance mediated by the escape mode of apoptosis. The phenomenon that BCL-2 family antagonized the apoptosis induced by antitumor drugs and then acquired drug resistance has been reported in the clinical treatment of hematologic lymphatic system tumors, breast cancer, lung cancer, gastric cancer and other diseases. Thus, specific inhibitors targeting anti-apoptotic members of the BCL-2 family have emerged with the development of research. In this paper, we systematically reviewed the regulation of apoptosis mediated by BCL-2 family and the drug resistance mediated by BCL-2 family. Meanwhile, we summarized the research advances of BCL-2 family specific inhibitors to provide new strategy for solving the problems on tumor therapeutic resistance and for finding new therapeutic targets in the future.
Citation: CHEN Cong, HAO Jianqi, PENG Haoning, LIU Lunxu. Research progress of BCL-2 family apoptotic regulation and its mediated drug resistance after antitumor drug therapy. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(1): 140-148. doi: 10.7507/1007-4848.202104023 Copy
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- 1. Kerr JF, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 1972, 26(4): 239-257.
- 2. Farbman AI. Electron microscope study of palate fusion in mouse embryos. Dev Biol, 1968, 18(2): 93-116.
- 3. Klion FM, Schaffner F. The ultrastructure of acidophilic "Councilman-like" bodies in the liver. Am J Pathol, 1966, 48(5): 755-767.
- 4. Su Z, Yang Z, Xu Y, et al. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer, 2015, 14: 48.
- 5. Mohammad RM, Muqbil I, Lowe L, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol, 2015, 35 Suppl(0): S78-S103.
- 6. Bakhshi A, Jensen JP, Goldman P, et al. Cloning the chromosomal breakpoint of t(14; 18) human lymphomas: Clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell, 1985, 41(3): 899-906.
- 7. Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell, 1986, 47(1): 19-28.
- 8. Maji S, Panda S, Samal SK, et al. Bcl-2 antiapoptotic family proteins and chemoresistance in cancer. Adv Cancer Res, 2018, 137: 37-75.
- 9. Youle RJ, Strasser A. The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol, 2008, 9(1): 47-59.
- 10. Elkholi R, Floros KV, Chipuk JE. The role of BH3-only proteins in tumor cell development, signaling, and treatment. Genes Cancer, 2011, 2(5): 523-537.
- 11. Pawlowski J, Kraft AS. Bax-induced apoptotic cell death. Proc Natl Acad Sci U S A, 2000, 97(2): 529-531.
- 12. Westphal D, Dewson G, Czabotar PE, et al. Molecular biology of Bax and Bak activation and action. Biochim Biophys Acta, 2011, 1813(4): 521-531.
- 13. Leu JI, Dumont P, Hafey M, et al. Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol, 2004, 6(5): 443-450.
- 14. Llambi F, Wang YM, Victor B, et al. BOK is a non-canonical BCL-2 family effector of apoptosis regulated by ER-associated degradation. Cell, 2016, 165(2): 421-433.
- 15. Yakovlev AG, Di Giovanni S, Wang G, et al. BOK and NOXA are essential mediators of p53-dependent apoptosis. J Biol Chem, 2004, 279(27): 28367-28374.
- 16. Grespi F, Soratroi C, Krumschnabel G, et al. BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis. Cell Death Differ, 2010, 17(11): 1672-1683.
- 17. Han J, Goldstein LA, Hou W, et al. Regulation of mitochondrial apoptotic events by p53-mediated disruption of complexes between antiapoptotic Bcl-2 members and Bim. J Biol Chem, 2010, 285(29): 22473-22483.
- 18. Rousalova I, Krepela E. Granzyme B-induced apoptosis in cancer cells and its regulation (review). Int J Oncol, 2010, 37(6): 1361-1378.
- 19. Kim H, Rafiuddin-Shah M, Tu HC, et al. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat Cell Biol, 2006, 8(12): 1348-1358.
- 20. Shukla S, Saxena S, Singh BK, et al. BH3-only protein BIM: An emerging target in chemotherapy. Eur J Cell Biol, 2017, 96(8): 728-738.
- 21. Esposti MD. The roles of Bid. Apoptosis, 2002, 7(5): 433-440.
- 22. Yu J, Zhang L. PUMA, a potent killer with or without p53. Oncogene, 2008, 27 Suppl 1(Suppl 1): S71-S83.
- 23. Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell, 2001, 7(3): 683-694.
- 24. Ploner C, Kofler R, Villunger A. Noxa: At the tip of the balance between life and death. Oncogene, 2008, 27 Suppl 1(Suppl 1): S84-S92.
- 25. Chipuk JE, Bouchier-Hayes L, Kuwana T, et al. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science, 2005, 309(5741): 1732-1735.
- 26. Jiang P, Du W, Wu M. P53 and Bad: Remote strangers become close friends. Cell Res, 2007, 17(4): 283-285.
- 27. Howells CC, Baumann WT, Samuels DC, et al. The Bcl-2-associated death promoter (BAD) lowers the threshold at which the Bcl-2-interacting domain death agonist (BID) triggers mitochondria disintegration. J Theor Biol, 2011, 271(1): 114-123.
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