[Wine-processed Chuanxiong Rhizoma enhances efficacy of aumolertinib against EGFRmutant non-small cell lung cancer xenografts in nude mouse brain].

Abstract

OBJECTIVE:

To investigate the effect of wine-processed Chuanxiong Rhizoma (WCR) for enhancing the efficacy of aumolertinib against xenografts of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) in the brain of nude mice.

METHODS:

In a co-culture system of hCMEC/D3 and PC9 NSCLC cells, the effect of aqueous extract of WCR (2 mg/mL) combined with aumolertinib (10 and 20 μmol/L) on apoptosis of PC9 cells was investigated using flow cytometry. The effects of WCR extract (0.5, 1, and 2 mg/mL) on transmembrane transport of 8 μmol/L aumolertinib was examined in ABCB1-MDCK monolayer cells. Western blotting was used to detect the expressions of the tight junction proteins related with blood- brain barrier integrity. A nude mouse model bearing NSCLC xenograft in the brain was established to observe the inhibitory effect of WCR (1 mg/g) combined with aumolertinib (10 mg/kg) on tumor growth.

RESULTS:

Compared with aumolertinib (20 μmol/L) alone, WCR extract (2 mg/mL) combined with aumolertinib significantly increased the apoptosis rate of PC9 cells by 21% (P < 0.01). The combined treatment with WCR (0.5, 1, 2 mg/mL) obviously increased apical-basolateral transport of aumolertinib in ABCB1-MDCK monolayer cells (P < 0.05) and significantly lowered the expression levels of zonula occludens-1, claudin-5 and P-glycoprotein (P < 0.05). In the tumor-bearing mice, compared with aumolertinib alone, the combined treatment with WCR and aumolertinib produced stronger inhibitory effect on tumor growth, improved weight loss, and prolonged the survival time of the nude mice (P < 0.05). Pathological examination showed that the combined treatment obviously increased the apoptosis rate of the tumor cells and alleviated neural injuries in the brain. Immunohistochemistry revealed that WCR treatment significantly reduced the expressions of ZO-1 and claudin-5 in the brain of the mice.

CONCLUSION:

WCR combined with aumolertinib shows stronger inhibitory effects against tumor xenografts of EGFR-mutant NSCLC possibly due to the effect of WCR in facilitating the transmembrane transport of aumolertinib by downregulating ZO-1, claudin-5 and P-glycoprotein expression.

• Authors: W Niu, X Rong, Q Zhao, X Liu, L Xu, S Li, X Li
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 43 Issue 3 Pg. 375-382 (Mar 20 2023) ISSN: 1673-4254 [Print] China
• PMID: 37087581 (Publication Type: English Abstract, Journal Article)

Chemical References

• aumolertinib
• Claudin-5
• ErbB Receptors

Topics

• Humans
• Mice
• Animals
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Mice, Nude
• Lung Neoplasms (drug therapy, pathology)
• Heterografts
• Wine
• Claudin-5 (metabolism)
• ErbB Receptors (metabolism)
• Blood-Brain Barrier (metabolism, pathology)
• Cell Line, Tumor