索拉非尼和依维莫司联合治疗在 DOX 荷瘤鼠模型中逆转多柔比星耐药性骨肉瘤。

Combination Treatment With Sorafenib and Everolimus Regresses a Doxorubicin-resistant Osteosarcoma in a PDOX Mouse Model.

机构信息

AntiCancer, Inc., San Diego, CA, U.S.A.

Department of Surgery, University of California, San Diego, CA, U.S.A.

出版信息

Anticancer Res. 2019 Sep;39(9):4781-4786. doi: 10.21873/anticanres.13662.

DOI:10.21873/anticanres.13662

PMID:31519579

Abstract

BACKGROUND/AIM: Osteosarcoma is a rare but recalcitrant type of bone cancer. To discover an effective therapy for osteosarcoma, we used a patient-derived orthotopic xenograft (PDOX) mouse model. A PDOX mouse model has been established for all major cancer types. Strong synergistic efficacy of sorafenib (SFN) and everolimus (EVL) has been demonstrated in several cancers. In the present study, we examined the efficacy of a SFN and EVL combination on a doxorubicin (DOX)-resistant osteosarcoma PDOX.

MATERIALS AND METHODS

The osteosarcoma PDOX models were randomly divided into five treatment groups, each containing six mice: Control; DOX; SFN; EVL; and a combination of SFN and EVL. Mice were treated for 14 days. To observe the efficacy of these treatments, tumor size and body weight were measured, and histological sections were analyzed.

RESULTS

Tumor growth regression was observed only in the mice treated with the combination of SFN-EVL. Histological analysis revealed necrosis with degenerative changes in tumors treated with a combination of SFN-EVL.

CONCLUSION

A SFN-EVL combination could be a novel effective treatment option for osteosarcoma.

摘要

背景/目的：骨肉瘤是一种罕见但难以治疗的骨癌。为了发现治疗骨肉瘤的有效方法，我们使用了患者来源的原位异种移植（PDOX）小鼠模型。PDOX 小鼠模型已被建立用于所有主要癌症类型。索拉非尼（SFN）和依维莫司（EVL）在几种癌症中表现出很强的协同疗效。在本研究中，我们研究了 SFN 和 EVL 联合治疗多柔比星（DOX）耐药骨肉瘤 PDOX 的疗效。