2021年9月
Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression.
Cancer chemotherapy and pharmacology
- 巻
- 88
- 号
- 3
- 開始ページ
- 513
- 終了ページ
- 524
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s00280-021-04310-5
BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.
- リンク情報
- ID情報
-
- DOI : 10.1007/s00280-021-04310-5
- PubMed ID : 34114067