Cyclopamine sensitizes multiple myeloma cells to circularly permuted TRAIL‑induced apoptosis

Wang,Huijuan; Geng,Chuanying; Zhou,Huixing; Zhang,Zhiyao; Chen,Wenming

doi:10.3892/ol.2021.12556

Cyclopamine sensitizes multiple myeloma cells to circularly permuted TRAIL‑induced apoptosis

Authors:
- Huijuan Wang
- Chuanying Geng
- Huixing Zhou
- Zhiyao Zhang
- Wenming Chen
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Affiliations: Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China
Published online on: February 17, 2021 https://doi.org/10.3892/ol.2021.12556
Article Number: 295

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Abstract

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a promising anti‑myeloma drug prototype. The aim of the present study was to investigate the synergistic effects of cyclopamine and circularly permuted TRAIL (CPT) on the proliferation and apoptosis of multiple myeloma cells. The results showed that the inhibitory effects of cyclopamine on the proliferation of human myeloma RPMI‑8226 and SKO‑007 cells were weak. RPMI‑8226 cells were sensitive to CPT; however, the proliferation of SKO‑007 cells was not effectively inhibited by CPT. SKO‑007 cells were thus considered resistant to cyclopamine and CPT and used for subsequent experiments. Treatment with a combination of cyclopamine and CPT significantly inhibited cell proliferation. Moreover, the Q value showed that cyclopamine combined with CPT could synergistically inhibit the proliferation of SKO‑007 cells. Cyclopamine increased CPT‑induced apoptosis in the SKO‑007 cells and exhibited a synergistic induction of apoptosis when combined with CPT. Moreover, the combination of cyclopamine and CPT decreased the ratio of myeloma stem cells. Quantitative PCR showed that cyclopamine decreased the mRNA expression levels of GLI1/GLI2/GLI3 and increased the expression levels of death receptor 4. In conclusion, the present study showed that a combination of cyclopamine and CPT exhibited synergistic effects on the inhibition of proliferation and induction of apoptosis in myeloma cells.

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