Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

Scientific Reports
Jing DuSichuan Xi

Abstract

Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the specificity of a Chinese herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling pathway to block NSCLC progression. Our study confirmed that aberrant activation of the SHH signal pathway conferred more proliferative and invasive phenotypes to human lung cancer cells. This study revealed that SBE specifically repressed SHH signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis via arresting cell cycle progression. We also found that SBE significantly sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH components in vitro and in vivo. Mechanistic investigations indicated that SBE transcriptionally and specifically downregulated SMO and consequently attenuated the activities of GLI1 and its downstream targets in SHH signaling pathway, which interacted with cell cycle checkpoint enzymes to arrest cell cycle progression and lead to cellular growth inhibition and migratio...Continue Reading

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Citations

Dec 24, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Siyu HeDaling Zhu
Mar 17, 2018·Cancer Chemotherapy and Pharmacology·Weiwei ChenJing Du
Aug 28, 2021·International Journal of Molecular Sciences·Ana María ZárateCristian O Salas

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Methods Mentioned

BETA
Flowcytometry
flow cytometry
xenograft
xenografts
PCR
transfection

Software Mentioned

ModFit
CompuSyn
Graphpad Prism
ImageJ
image J
Olympus
Image Lab

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