Development of Stemness in Cancer Cell Lines Resistant to the Anticancer Effects of Zoledronic Acid

被引：0
作者：
Yoshiyama, Akira [1 ]
Morii, Takeshi [1 ]
Ohtsuka, Kouki [2 ]
Ohnishi, Hiroaki [2 ]
Tajima, Takashi [1 ,3 ]
Aoyagi, Takayuki [1 ]
Mochizuki, Kazuo [1 ]
Satomi, Kazuhiko [1 ]
Ichimura, Shoichi [1 ]
机构：
[1] Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
[2] Kyorin Univ, Fac Med, Dept Clin Lab Med, Mitaka, Tokyo, Japan
[3] Natl Canc Res Ctr, Res Inst, Dept Drug Design Proteome Area Res, Chuuo Ku, Tokyo, Japan
来源：
ANTICANCER RESEARCH | 2016年 / 36卷 / 02期
关键词：
Osteosarcoma; lung cancer; drug resistance; zoledronic acid; cancer stem cells; DRUG-RESISTANCE; HUMAN OSTEOSARCOMA; SELF-RENEWAL; C-MYC; EXPRESSION; INHIBITION; CHONDROSARCOMA; SENSITIVITY; LEUKEMIA; PATHWAY;
D O I：
暂无
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: Drug resistance is closely related to cancer cell stemness, that is acquired along with resistance to various anticancer agents. However, this has not been investigated as a potential mechanism underlying cancer cell resistance to zoledronate, that is used to suppress bone metastasis. Materials and Methods: Zoledronate-resistant A549 lung cancer and MG63 osteosarcoma cell lines were established by repeated treatment with sub-lethal concentrations of zoledronate. Expression levels of the stem cell marker NANOG, cMYC, octamer-binding transcription factor 4, and sex-determining region Y-box 2 were evaluated and sphere formation was compared between parental and resistant cell lines. Tumourigenicity was assessed in vivo. Results: Stem cell marker expression was up-regulated and sphere formation was enhanced in resistant compared to parental cells and showed greater tumour formation capacity in mice. Conclusion: Repeated treatment of malignant tumour cell lines with zoledronate, induces the development of drug resistance and stemness.
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页码：625 / 631
页数：7
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