2. Academic Validation
  3. Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer

Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer

  • Acta Pharm Sin B. 2023 Mar;13(3):967-981. doi: 10.1016/j.apsb.2022.03.003.
Senlin Li 1 2,  Siyu Chen 3,  Zhihui Dong 1,  Xingdong Song 2,  Xiuling Li 1,  Ziqi Huang 2,  Huiru Li 2,  Linzhuo Huang 1,  Ganyuan Zhuang 1,  Ran Lan 2,  Mingyan Guo 4,  Wende Li 3,  Phei Er Saw 1,  Lei Zhang 2
Affiliations

Affiliations

  • 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 Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 3 Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou, 510663, China.
  • 4 Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
PMID: 36970197 DOI: 10.1016/j.apsb.2022.03.003
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.

Keywords

Chemoresistance; Combination therapy; Hepatocellular carcinoma; Nanomedicine; Nanoparticle; RNA interference; Tubulin folding cofactor E; siRNA delivery.

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