自噬与凋亡在骨肉瘤中的作用
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摘要
骨肉瘤是儿童和青少年中最常见的原发性骨肿瘤,其恶性程度高,严重影响患者的生存。虽然手术和多靶点化疗的联合治疗使得患者整体的生存率有了大幅度的提高,但化疗耐药仍然是骨肉瘤治疗的阻碍。骨肉瘤化疗耐药与其在发生发展过程中的凋亡和自噬等有一定关系。现在骨肉瘤中细胞凋亡、自噬的机制以及相互作用已经被初步探索,参与细胞凋亡、自噬的分子靶点、介质及相关机制已经开始研究,这对缓解骨肉瘤治疗过程中的化学耐药指导引领新的方向。
Osteosarcoma is the most common primary bone tumor in children and adolescents with high malignancy,seriously affecting the survival of the patients. Although the combination of surgery and multi-target chemotherapy has greatly improved the overall survival rate,chemotherapy resistance is still an obstacle to the treatment. Chemotherapy resistance of osteosarcoma is related to apoptosis and autophagy during its development. The mechanism of apoptosis and autophagy and the relationship between them have been preliminarily explored in osteosarcoma,and the molecular targets,medium and relevant mechanisms of apoptosis,autophagy have begun to be studied,which provides a new direction for relieving the chemical resistance during osteosarcoma treatment.
Osteosarcoma is the most common primary bone tumor in children and adolescents with high malignancy,seriously affecting the survival of the patients. Although the combination of surgery and multi-target chemotherapy has greatly improved the overall survival rate,chemotherapy resistance is still an obstacle to the treatment. Chemotherapy resistance of osteosarcoma is related to apoptosis and autophagy during its development. The mechanism of apoptosis and autophagy and the relationship between them have been preliminarily explored in osteosarcoma,and the molecular targets,medium and relevant mechanisms of apoptosis,autophagy have begun to be studied,which provides a new direction for relieving the chemical resistance during osteosarcoma treatment.
引文
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[33]Guo S,Bai R,Liu W,et al.miR-22 inhibits osteosarcoma cell proliferation and migration by targeting HMGB1 and inhibiting HMGB1-mediated autophagy[J].Tumour Biol,2014,35(7):7025-7034.
[34]Huang J,Liu K,Yu Y,et al.Targeting HMGB1-mediated autophagy as a novel therapeutic strategy for osteosarcoma[J].Autophagy,2012,8(2):275-277.
[35]Yang C,Gao R,Wang J,et al.High-mobility group nucleosome-binding domain 5 increases drug resistance in osteosarcoma through upregulating autophagy[J].Tumour Biol,2014,35(7):6357-6363.
[36]Chang Z,Huo L,Li K,et al.Blocked autophagy by miR-101enhances osteosarcoma cell chemosensitivity in vitro[J].Sci World J,2014,2014:794756.
[37]Huang WP,Klionsky DJ.Autophagy in yeast:A review of the molecular machinery[J].Cell Struct Funct,2002,27(6):409-420.
[38]Zhang MS,Niu FW,Li K.Proflavin suppresses the growth of human osteosarcoma MG63 cells through apoptosis and autophagy[J].Oncol Lett,2015,10(1):463-468.
[39]Li HY,Zhang J,Sun LL,et al.Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells:An in vitro and in vivo study[J].Cell Death Dis,2015,6:e1604.
[40]Zhang W,Li Q,Song C,et al.Knockdown of autophagy-related protein 6,Beclin1,decreases cell growth,invasion,and metastasis and has a positive effect on chemotherapy-induced cytotoxicity in osteosarcoma cells[J].Tumour Biol,2015,36(4):2531-2539.
[41]Mori M,Hitora T,Nakamura O,et al.Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells[J].Int J Oncol,2015,46(1):47-54.
[42]Horie R,Nakamura O,Yamagami Y,et al.Apoptosis and antitumor effects induced by the combination of an m TOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells[J].Int J Oncol,2016,48(1):37-44.
[43]Ji GR,Yu NC,Xue X,et al.PERK-mediated autophagy in osteosarcoma cells resists ER stressinduced cell apoptosis[J].Int JBiol Sci,2015,11(7):803-812.
[2]Daw NC,Chou AJ,Jaffe N,et al.Recurrent osteosarcoma with a single pulmonary metastasis[J].Br J Cancer,2015,112(2):278-282.
[3]Friebele JC,Peck J,Pan X,et al.Osteosarcoma:A meta-analysis and review of the literature[J].Am J Orthop(Belle Mead NJ),2015,44(12):547-553.
[4]Salunke AA,Chen Y,Tan JH,et al.Does a pathological fracture affect the prognosis in patients with osteosarcoma of the extremities?A systematic review and meta-analysis[J].Bone Joint J,2014,96-B(10):1396-1403.
[5]Yu W,Tang L,Lin F,et al.Highintensity focused ultrasound:noninvasive treatment for local unresectable recurrence of osteosarcoma[J].Surg Oncol,2015,24(1):9-15.
[6]Fu HL,Shao L,Wang Q,et al.A systematic review of p53 as a biomarker of survival in patients with osteosarcoma[J].Tumour Biol,2013,34(6):3817-3821.
[7]Shin SH,Jeong HJ,Han I,et al.Osteosarcoma and chondrosarcoma of the shoulder:Site specific comparative analysis[J].Orthopedics,2013,36(2):e179-185.
[8]Baranski Z,Booij TH,Cleton-Jansen AM,et al.Avenmediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma[J].J Pathol,2015,236(3):348-359.
[9]Li S,Sun W,Wang H,et al.Research progress on the multidrug resistance mechanisms of osteosarcoma chemotherapy and reversa[J].Tumour Biol,2015,36(3):1329-1338.
[10]Argun M,T9k L,Uˇgu AC,et al.Melatonin and amfenac modulate calcium entry,apoptosis,and oxidative stress in ARPE-19 cell culture exposed to blue light irradiation(405 nm)[J].Eye(Lond),2014,28(6):752-760.
[11]He H,Ni J,Huang J.Molecular mechanisms of chemoresistance in osteosarcoma(Review)[J].Oncol Lett,2014,7(5):1352-1362.
[12]Song B,Wang Y,Xi Y,et al.Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells[J].Oncogene,2009,28(46):4065-4074.
[13]Tian Y,Zhang YZ,Chen W.MicroRNA-199a-3p and microRNA-34a regulate apoptosis in human osteosarcoma cells[J].Biosci Rep,2014,34(4).pii:e00132.
[14]Liu W,Xu G,Liu H,et al.MicroRNA-490-3p regulates cell proliferation and apoptosis by targeting HMGA2 in osteosarcoma[J].FEBS Lett,2015,589(20 Pt B):3148-3153.
[15]Zhao H,Li M,Li L,et al.MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation,migration and invasion,and promotes apoptosis[J].PLo S One,2013,8(12):e83571.
[16]Tian K,Di R,Wang L.MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma[J].Cancer Gene Ther,2015,22(7):351-359.
[17]Maugg D,Rothenaigner I,Schorpp K,et al.New small molecules targeting apoptosis and cell viability in osteosarcoma[J].PLo SOne,2015,10(6):e0129058.
[18]Wang XF,Wang J.Icaritin suppresses the proliferation of human osteosarcoma cells in vitro by increasing apoptosis and decreasing MMP expression[J].Acta Pharmacol Sin,2014,35(4):531-539.
[19]Ding L,He S,Sun X.HSP70 desensitizes osteosarcoma cells to baicalein and protects cells from undergoing apoptosis[J].Apoptosis,2014,19(8):1269-1280.
[20]Hanikoglu F,Cort A,Ozben H,et al.Epoxomicin sensitizes resistant osteosarcoma cells to TRAIL induced apoptosis[J].Anticancer Agents Med Chem,2015,15(4):527-533.
[21]Chipoy C,Brounais B,Trichet V,et al.Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53[J].Oncogene,2007,26(46):6653-6664.
[22]Roos A,Satterfield L,Zhao S,et al.Loss of Runx2 sensitises osteosarcoma to chemotherapy-induced apoptosis[J].Br J Cancer,2015,113(9):1289-1297.
[23]Guan H,Tan P,Xie L,et al.FOXO1 inhibits osteosarcoma oncogenesis via Wnt/beta-catenin pathway suppression[J].Oncogenesis,2015,4:e166.
[24]Lu DF,Wang YS,Li C,et al.Actinomycin D inhibits cell proliferations and promotes apoptosis in osteosarcoma cells[J].Int J Clin Exp Med,2015,8(2):1904-1911.
[25]Lv YF,Yan GN,Meng G,et al.Enhancer of zeste homolog 2 silencing inhibits tumor growth and lung metastasis in osteosarcoma[J].Sci Rep,2015,5:12999.
[26]Li S,Wang L,Hu Y,et al.Autophagy regulators as potential cancer therapeutic agents:A review[J].Curr Top Med Chem,2015,15(8):720-744.
[27]de Iriarte Rodríguez R,Pulido S,Rodriguez-de la Rosa L,et al.Age-regulated function of autophagy in the mouse inner ear[J].Hear Res,2015,330(Pt A):39-50.
[28]Miao XD,Cao L,Zhang Q,et al.Effect of PI3K-mediated autophagy in human osteosarcoma MG63 cells on sensitivity to chemotherapy with cisplatin[J].Asian Pac J Trop Med,2015,8(9):731-738.
[29]Liu Y,Zhao L,Ju Y,et al.A novel androstenedione derivative induces ROS-mediated autophagy and attenuates drug resistance in osteosarcoma by inhibiting macrophage migration inhibitory factor(MIF)[J].Cell Death Dis,2014,5:e1361.
[30]Meschini S,Condello M,Calcabrini A,et al.The plant alkaloid voacamine induces apoptosis-independent autophagic cell death on both sensitive and multidrug resistant human osteosarcoma cells[J].Autophagy,2008,4(8):1020-1033.
[31]Yang C,Shogren KL,Goyal R,et al.RNA-dependent protein kinase is essential for 2-methoxyestradiol-induced autophagy in osteosarcoma cells[J].PLo S One,2013,8(3):e59406.
[32]Li X,Wang S,Chen Y,et al.miR-22 targets the 3'UTR of HMGB1 and inhibits the HMGB1-associated autophagy in osteosarcoma cells during chemotherapy[J].Tumour Biol,2014,35(6):6021-6028.
[33]Guo S,Bai R,Liu W,et al.miR-22 inhibits osteosarcoma cell proliferation and migration by targeting HMGB1 and inhibiting HMGB1-mediated autophagy[J].Tumour Biol,2014,35(7):7025-7034.
[34]Huang J,Liu K,Yu Y,et al.Targeting HMGB1-mediated autophagy as a novel therapeutic strategy for osteosarcoma[J].Autophagy,2012,8(2):275-277.
[35]Yang C,Gao R,Wang J,et al.High-mobility group nucleosome-binding domain 5 increases drug resistance in osteosarcoma through upregulating autophagy[J].Tumour Biol,2014,35(7):6357-6363.
[36]Chang Z,Huo L,Li K,et al.Blocked autophagy by miR-101enhances osteosarcoma cell chemosensitivity in vitro[J].Sci World J,2014,2014:794756.
[37]Huang WP,Klionsky DJ.Autophagy in yeast:A review of the molecular machinery[J].Cell Struct Funct,2002,27(6):409-420.
[38]Zhang MS,Niu FW,Li K.Proflavin suppresses the growth of human osteosarcoma MG63 cells through apoptosis and autophagy[J].Oncol Lett,2015,10(1):463-468.
[39]Li HY,Zhang J,Sun LL,et al.Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells:An in vitro and in vivo study[J].Cell Death Dis,2015,6:e1604.
[40]Zhang W,Li Q,Song C,et al.Knockdown of autophagy-related protein 6,Beclin1,decreases cell growth,invasion,and metastasis and has a positive effect on chemotherapy-induced cytotoxicity in osteosarcoma cells[J].Tumour Biol,2015,36(4):2531-2539.
[41]Mori M,Hitora T,Nakamura O,et al.Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells[J].Int J Oncol,2015,46(1):47-54.
[42]Horie R,Nakamura O,Yamagami Y,et al.Apoptosis and antitumor effects induced by the combination of an m TOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells[J].Int J Oncol,2016,48(1):37-44.
[43]Ji GR,Yu NC,Xue X,et al.PERK-mediated autophagy in osteosarcoma cells resists ER stressinduced cell apoptosis[J].Int JBiol Sci,2015,11(7):803-812.