具有特殊抑制因子CBT-1®的目标分子ABCB1和ABCC1可以克服骨肉瘤中的药物耐药性

Title:Targeting ABCB1 and ABCC1 with their Specific Inhibitor CBT-1^® can Overcome Drug Resistance in Osteosarcoma

Volume: 16 Issue: 3

Author(s): Marilu Fanelli, Claudia Maria Hattinger, Serena Vella, Elisa Tavanti, Francesca Michelacci, and Beth Gudeman, Daryl Barnett, Piero Picci and Massimo Serra

Affiliation:

关键词: ABC转运体，化疗增敏、化学疗法、药物耐药性、骨肉瘤、特定治疗方案。

摘要: Clinical treatment response achievable with conventional chemotherapy in high-grade osteosarcoma (OS) is severely limited by the presence of intrinsic or acquired drug resistance, which in previous studies has been mainly addressed for overexpression of ABCB1 (MDR1/P-glycoprotein). This study was aimed to estimate the impact on OS drug resistance of a group of ATP binding cassette (ABC) transporters, which in other human tumors have been associated with unresponsiveness to the drugs that represent the backbone of multidrug treatment regimens for OS (doxorubicin, methotrexate, cisplatin).

By using a group of 6 drug-sensitive and 20 drug-resistant human OS cell lines, the most relevant transporter which proved to be associated with the degree of drug resistance in OS cells, in addition to ABCB1, was ABCC1. We therefore evaluated the in vitro activity of the orally administrable ABCB1/ABCC1 inhibitor CBT-1^® (Tetrandrine, NSC-77037). We found that in our OS cell lines this agent was able to revert the ABCB1/ABCC1-mediated resistance against doxorubicin, as well as against the drugs used in second-line OS treatments that are substrates of these transporters (taxotere, etoposide, vinorelbine). Our findings indicated that inhibiting ABCB1 and ABCC1 with CBT-1^®, used in association with conventional chemotherapeutic drugs, may become an interesting new therapeutic option for unresponsive or relapsed OS patients.

Cite this article as:

Marilu Fanelli, Claudia Maria Hattinger, Serena Vella, Elisa Tavanti, Francesca Michelacci, and Beth Gudeman, Daryl Barnett, Piero Picci and Massimo Serra , Targeting ABCB1 and ABCC1 with their Specific Inhibitor CBT-1^® can Overcome Drug Resistance in Osteosarcoma, Current Cancer Drug Targets 2016; 16 (3) . https://dx.doi.org/10.2174/1568009616666151106120434