Page 64 - 《中国药房》2021年第4期
P. 64
PTEN 是具有磷酸酶活性的抑癌基因,在多种肿瘤 pression is associated with acquired chemo-resistance of
细胞中异常表达,对PI3K/Akt信号通路起到负向调节作 cisplatin in osteosarcoma cells[J]. Hum Cell,2017. DOI:
[21]
用 ,上调 PTEN 基因的表达或使用 PI3K/Akt/mTOR 信 10.1007/s13517-017-0169-9.
号通路抑制剂,均可逆转肿瘤细胞的多药耐药,从而提 [ 9 ] LINDSE YB,MARKEL JE,KLEINERMAN ES. Osteo-
sarcoma overview[J]. Rheumatol Ther,2017,4(1):25-43.
高化疗的效果。P-gp是相对分子质量为170 kDa的跨膜
[10] 耿帅,赵育林,曾凯,等.丹皮酚的研究进展[J].中国新药
转运糖蛋白,由 ABCB1 基因编码,具有 12 个跨膜区和 2
与临床杂志,2016,35(5):310-313.
个细胞内腺苷三磷酸(ATP)连接点。肿瘤细胞长期接触
[11] 吴琪,吴倩,周晓红,等.丹皮酚对强直性脊柱炎模型小鼠
亲脂类化疗药物,ABCB1 基因被诱导扩增,P-gp 被大量
Wnt 和 BMP/Smad 信号转导通路的影响[J].中国药房,
表达,ATP 跨膜转运作用将药物转运到细胞外,使细胞 2018,29(11):1500-1504.
内药物集聚减少,作用靶点部位的药物浓度降低,导致 [12] TSAI CY,KAPOOR M,HUANG YP,et al. Synthesis and
化疗效果下降或消失。P-gp 在多种恶性肿瘤中均呈较 evaluation of aminothiazole-paeonol derivatives as poten-
高表达状态 。本研究结果显示,丹皮酚联合顺铂可明 tial anticancer agents[J]. Molecules,2016. DOI:10.3390/
[22]
显下调骨肉瘤细胞PI3KCA、Akt、mTOR mRNA的表达, molecules21020145.
上 调 P-gp、PTEN mRNA 表 达 ,从 而 阻 断 PI3K/Akt/ [13] 李禀枢,付琼,孙青,等.丹皮酚对人卵巢癌细胞 A2780s
mTOR信号通路靶基因表达,发挥抑瘤作用。其中P-gp 增殖的影响[J].肿瘤,2011,31(2):122-125.
mRNA在低、高浓度联用组表达的升高可能与P-gp介导 [14] 张传凤,颜贵明,马克龙.丹皮酚抗癌作用及机制近五年
[23]
的多药耐药有关 ,具体机制还需进一步深入研究。 研究进展[J].辽宁中医药大学学报,2019,21(10):158-
综上所述,丹皮酚联合顺铂可通过调控骨肉瘤细胞 161.
[15] SONG RP,TIAN K,WANG WD,et al. P53 suppresses
PI3K/Akt/mTOR 信 号 通 路 中 PI3KCA、Akt、mTOR、
cell proliferation,metastasis,and angiogenesis of osteosar-
P-gp、TEN mRNA 的表达而抑制骨肉瘤细胞的增殖、诱
coma through inhibition of the PI3K/Akt/mTOR path-
导其凋亡,下一步可深入探讨丹皮酚联合顺铂对骨肉瘤
way[J]. Int J Surg,2015. DOI:10.1016/j.ijsu.2015.04.050.
细胞多药耐药的影响。 [16] 刘盖为,代国,郭卫春.顺铂影响骨肉瘤143B细胞Notch
参考文献 信号通路的实验研究[J].临床和实验医学杂志,2017,16
[ 1 ] GIANFERANTE DM,MIRABELLO L,SAVAGE SA. (3):209-213.
Germline and somatic genetics of osteosarcoma-connect- [17] 李明,谭诗云.丹皮酚通过下调COX-2表达及PGE2合成
ing aetiology,biology and therapy[J]. Nat Rev Endocri- 抑制大肠癌细胞增殖及诱导细胞凋亡[J].胃肠病学和肝
nol,2017. DOI:10.1038/nrendo.2017.16. 病学杂志,2017,26(2):128-133.
[ 2 ] HUO YQ,LI QB,WANG XQ,et al. MALAT1 predicts [18] EDWIN C,FRANCIS H,LAURA M,et al. High-through-
poor survival in osteosarcoma patients and promotes cell put genotyping in osteosarcoma identifies multiple muta-
metastasis through associating with EZH2[J]. Oncotarget, tions in phosphoinositide-3-kinase and other oncogenes[J].
2017,8(29):46993-47006. Cancer,2012,118(11):2905-2914.
[ 3 ] SHAIKH AB,LI FF,LI M,et al. Present advances and fu- [19] CHEAIB B,AUGUSTE A,LEARY A. The PI3K/Akt/
ture perspectives of molecular targeted therapy for osteo- mTOR pathway in ovarian cancer:therapeutic opportuni-
sarcoma[J]. Int J Mol Sci,2016. DOI:10.3390/ijms170- ties and challenges[J]. Chin J Cancer,2015,34(1):4-16.
40506. [20] PACHOW D,WICK W,GUTMANN DH,et al. The
[ 4 ] ZHANG Y,YANG J,ZHAO N,et al. Progress in the che- mTOR signaling pathway as a treatment target for intracra-
motherapeutic treatment of osteosarcoma[J]. Oncol Lett, nial neoplasms[J]. Neuro Oncol,2015,17(2):189-199.
2018,16(5):6228-6237. [21] XI YM,CHEN Y. Oncogenic and therapeutic targeting of
[ 5 ] DASARI S,TCHOUNWOU PB. Cisplatin in cancer thera- PTEN loss in bone malignancies[J]. J Cell Biochem,2015.
py:molecular mechanisms of action[J]. Eur J Pharmacol, DOI:10.1002/jcb.25159.
2014. DOI:10.1016/j.ejphar.2014.07.025. [22] LIN LF,WU MH,PIDUGU VK,et al. P-glycoprotein at-
[ 6 ] LUETKE A,MEYERS PA,LEWIS I,et al. Osteosarcoma tenuates DNA repair activity in multidrug-resistant cells
treatment:where do we stand:a state of the art review[J]. by acting through the Cbp-Csk-Src cascade[J]. Oncotar-
Cancer Treat Rev,2014,40(4):523-532. get,2017. DOI:10.18632/oncotarget.15065.
[ 7 ] SHANMUGAM V,CHIEN YH,CHENG YS,et al. Oligo- [23] GAO Y,LIAO YF,SHEN JK,et al. Evaluation of P-glyco-
nucleotides-assembled au nanorod-assisted cancer photo- protein (Pgp) expression in human osteosarcoma by
thermal ablation and combination chemotherapy with tar- high-throughput tissue microarray[J]. J Orthop Res,2016,
geted dual-drug delivery of doxorubicin and cisplatin pro- 34(6):1606-1612.
drug[J]. Acs Appl Mater Inter,2014,6(6):4382-4393. (收稿日期:2020-11-09 修回日期:2021-01-18)
[ 8 ] SUN XL,WEI Q,CHENG J,et al. Enhanced stim1 ex- (编辑:邹丽娟)
·442 · China Pharmacy 2021 Vol. 32 No. 4 中国药房 2021年第32卷第4期