Mechanism of Targeting the Hedgehog Signaling Pathway against Chemotherapeutic Resistance in Multiple Myeloma

Yuefeng Zhang; Guoli Yao; Xinxin Yang; Tao Qiu; Sheng Wang

doi:10.1155/2022/1399697

Mechanism of Targeting the Hedgehog Signaling Pathway against Chemotherapeutic Resistance in Multiple Myeloma

J Oncol. 2022 Jun 29:2022:1399697. doi: 10.1155/2022/1399697. eCollection 2022.

Authors

Yuefeng Zhang¹, Guoli Yao¹, Xinxin Yang¹, Tao Qiu¹, Sheng Wang¹

Affiliation

¹ Department of Hematology, First People's Hospital of Linping District, Hangzhou 311100, Zhejiang, China.

Abstract

Objective: The aim of this study was to explore the relationship between the Hedgehog signaling pathway and drug resistance in multiple myeloma.

Methods: The human myeloma cell line RPMI 8266 was taken as the research object. An azithromycin (AZM)-resistant cell line RPMI 8226/R was constructed, and GENT61 was used to block the Hedgehog signaling pathway. Cells were rolled into RPMI 8226/S (S group), RPMI 8226/R (R group), GENT61+RPMI 8226/S (GENT61+S group), and GENT61+RPMI 8226/R (GENT61+R group). The proliferation of cells in each group was assessed, and the expression of patched homolog 1 (PTCH1), zinc finger-containing transcription factors 1 (GLI1), GLI2, hair-division associated enhancer 1 (Hes1), and sonic hedgehog factor (SHH) in each group was detected. Interleukin (IL)-6 and vascular endothelial growth factor (VEGF) were measured.

Results: Compared with the S group, the expression levels of PTCH1, GLI2, Hes1, and SHH and the contents of IL-6 and VEGF in the R group were greatly increased, while the expression level of GLI1 was notably decreased (P < 0.05). Compared with the R group, the GENT61+R group greatly increased cell proliferation inhibition. However, the expression levels of PTCH1, GLI2, Hes1, and SHH, and the contents of IL-6 and VEGF were notably decreased, while GLI1 expression levels were greatly increased (P < 0.05).

Conclusion: AZM-resistant multiple myeloma was closely associated with the Hedgehog signaling pathway activation, and blocking the Hedgehog signaling pathway can be used as a therapeutic target to improve drug resistance in multiple myeloma.