Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer.
10.1016/j.apsb.2022.03.003
- Author:
Senlin LI
1
;
Siyu CHEN
2
;
Zhihui DONG
1
;
Xingdong SONG
3
;
Xiuling LI
1
;
Ziqi HUANG
3
;
Huiru LI
3
;
Linzhuo HUANG
1
;
Ganyuan ZHUANG
1
;
Ran LAN
3
;
Mingyan GUO
4
;
Wende LI
2
;
Phei Er SAW
1
;
Lei ZHANG
3
Author Information
1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
2. Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou, 510663, China.
3. Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
4. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
- Publication Type:Journal Article
- Keywords:
Chemoresistance;
Combination therapy;
Hepatocellular carcinoma;
Nanomedicine;
Nanoparticle;
RNA interference;
Tubulin folding cofactor E;
siRNA delivery
- From:
Acta Pharmaceutica Sinica B
2023;13(3):967-981
- CountryChina
- Language:English
-
Abstract:
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
