Sensitizing effect of d-borneol on cisplatin-resistant NSCLC based on transcriptomics and its mechanism
- Author:
Jin-Xiu LI
1
;
Jia-Jun WANG
1
;
Rong MA
1
;
Qian XIE
1
;
Jian WANG
1
;
Nan ZENG
1
;
Jin-Xiu LI
2
;
Jia-Jun WANG
2
;
Rong MA
2
;
Qian XIE
2
;
Jian WANG
2
;
Nan ZENG
2
;
Dao-Yin GONG
3
Author Information
- Publication Type:Journal Article
- Keywords: cell cycle; d-borneol; drug resistance; eisplatin; lung cancer; RNA sequencing
- From: Chinese Pharmacological Bulletin 2023;39(6):1105-1114
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the key targets of d-borneol combined with eisplatin for sensitization of cisplatin-resistant NCSLC cells by RNA-Seq and verify its mechanism. Methods Cisplatin-resistant human large cell lung cancer cells (H460/CDDP) were inoculated into the right armpit of male BALB/c nude mice (4 weeks old) to construct a xenograft tumor model. Then they were randomly divided into control group, vehicle group, eisplatin group, and combination group (d-borneol + eisplatin) with 6 nude mice and treated for 14 d. After last administration of 24 h, the tumor tissue was taken for RNA-Seq. And then real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to verify the expression of cell cycle-related molecules. Results RNA-seq analysis showed that there were significant differences in gene expression between the eisplatin group and combined group, and they were significantly enriched in cell cycle. RT-PCR and IHC results showed that d-borneol combined with eisplatin could significantly inhibit the expressions of cyclins (cyclin A2, cyclin D3) and cyclin-dependent kinases (CDK2, CDK6) and promote the expression of its upstream molecular cyclin-dependent kinase inhibitor CD-KI (P21, P27) (P<0. 05, P<0.01). Conclusions d-Borneol increases the sensitivity of eisplatin by increasing the expression of P21 and P27 and inhibiting the expression of cyclinA2/D3 and CDK2/6 to induce cell cycle arrest and inhibit the malignant proliferation of H460/CDDP cells, thereby achieving the effect of anti-drug sensitization.
