Combination of Novel Antimyeloma Prototype and Cyclopamine Under Study
Posted: Friday, May 21, 2021
A recombinant version of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), called circularly permuted TRAIL (CPT), appears to be a novel antimyeloma prototype. In previous clinical trials, CPT has exhibited antitumor activity with no effects on normal cells, although some patients develop resistance to the treatment. Cyclopamine is a Hedgehog signal pathway inhibitor and has exhibited synergistic therapeutic effects when combined with anticancer drugs. Thus, Wenming Chen, MD, of Capital Medical University, Beijing, and colleagues reported that the combination of CPT and cyclopamine appeared to inhibit the proliferation of myeloma cells and induce apoptosis effectively. The study was published in Oncology Letters.
The researchers tested the synergistic effects of cyclopamine and CPT on the proliferation and apoptosis of cancer cells. Two myeloma cell lines were tested: RPMI-8266 and SKO-007.
Cyclopamine demonstrated weak inhibitory effects on the proliferation of RPMI-8226 and SKO-007 cells. CPT, alone, effectively inhibited RPMI-8226 cells; however, neither cyclopamine nor CPT therapies were effective when used independently to treat SKO-007 cells.
The combination of cyclopamine and CPT significantly inhibited cancer cell proliferation, the researchers reported. Cyclopamine appeared to increase CPT-induced apoptosis in the SKO-007 cell line. The q value indicated that cyclopamine in combination with CPT might synergistically inhibit the proliferation of SKO-007 cells. The combination treatment also decreased the ratio of myeloma stem cells, which are considered an underlying factor of drug resistance and a potential reason for relapse. The quantitative polymerase chain reaction tests demonstrated that cyclopamine increased the expression levels of death receptor 4, potentially explaining the increased sensitivity of SKO-007 to CPT.
“Further experiments may better reveal the mechanisms underlying the synergistic effects,” the authors concluded.
Disclosure: The study authors reported no conflicts of interest.
