Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.
Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.
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DOI：
10.1111/j.1582-4934.2008.00360.x
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发表时间：
2009-07
影响因子：
5.3
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Chen T;Li M;Zhang R;Wang H
本研究旨在确定青蒿素（ARS）及其衍生物对人卵巢癌细胞的作用，以评估其作为单独使用或与常规癌症化疗药物联合使用的新型化疗药物的潜力，并研究其潜在的作用机制。将人卵巢癌细胞（A2780和OVCAR-3）和永生化的非致瘤性人卵巢表面上皮细胞（IOSE 144）暴露于四种ARS化合物用于细胞毒性测试。在体外和体内的抗肿瘤作用和可能的潜在机制的双氢青蒿素（DHA），最有效的化合物，进一步确定在卵巢癌细胞。ARS化合物对人卵巢癌细胞具有强的细胞毒性，对非致瘤性卵巢表面上皮（OSE）细胞的影响最小。DHA单独给药或与卡铂联合给药可抑制卵巢癌细胞的生长，推测是通过死亡受体介导的半胱天冬酶依赖性凋亡途径。在体内卵巢A2780和OVCAR-3异种移植肿瘤模型中也观察到这些作用。总之，ARS衍生物，特别是DHA，在体外和体内对卵巢癌细胞表现出显著的抗癌活性，对非致瘤性人OSE细胞的毒性最小，表明它们可能是有前途的卵巢癌治疗剂，单独使用或与常规化疗联合使用。
The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.
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影响因子：
3
作者：
Chen, HH;Zhou, HJ;Wu, GD
通讯作者：
Wu, GD
DOI：
10.1007/s00432-005-0052-x
发表时间：
2006-02-01
影响因子：
3.6
作者：
Kim, SJ;Kim, MS;Lee, SH
通讯作者：
Lee, SH
影响因子：
56.9
作者：
KLAYMAN, DL
通讯作者：
KLAYMAN, DL
影响因子：
9.7
作者：
Lai, H;Singh, NP
通讯作者：
Singh, NP
影响因子：
5.8
作者：
Efferth, T;Olbrich, A;Bauer, R
通讯作者：
Bauer, R