# Antitumor Effects of Sesamin via the LincRNA-p21/STAT3 Axis in Human Bladder Cancer: Inhibition of Metastatic Progression and Enhanced Chemosensitivity

**Authors:** Chao-Yen Ho, Thomas I-Sheng Hwang, Pei-Wen Peng, Te-Fu Tsai, Kuang-Yu Chou, Hung-En Chen, Peng-Hui Chang, Wei-Chien Huang, Chung-Hua Hsu, Tsai-Ju Chien, An-Chen Chang

PMC · DOI: 10.7150/ijbs.103274 · International Journal of Biological Sciences · 2025-03-31

## TL;DR

Sesamin, a compound from sesame oil, may help treat bladder cancer by reducing tumor spread and improving response to chemotherapy.

## Contribution

This study reveals that sesamin inhibits bladder cancer progression via the lincRNA-p21/STAT3 axis and enhances chemosensitivity.

## Key findings

- Sesamin inhibits cell viability and tumor formation in bladder cancer.
- Sesamin reduces MMP2 expression and tumor cell migration by downregulating STAT3.
- LincRNA-p21 mediates sesamin's effects, and combining sesamin with a PARP inhibitor enhances chemotherapy sensitivity.

## Abstract

Bladder cancer (BC) ranks as the tenth most common malignancy worldwide, with high recurrence and progression rates despite current treatments. The matrix metalloproteinases (MMPs), particularly MMP2, play critical roles in tumor invasion and metastasis, contributing to poor prognosis. The p53-induced long noncoding RNA (lncRNA) lincRNA-p21, which acts as a tumor suppressor, has been implicated in various cancers, but its role in BC remains unclear. Sesamin, a bioactive lignan derived from sesame oil, has shown promise as a chemopreventive agent with multiple antitumor effects. In this study, sesamin was found to significantly inhibit cell viability in vitro and tumor formation in vivo. Additionally, sesamin inhibits MMP2 expression by downregulating the STAT3 signaling pathway, leading to reduced tumor cell migration, invasion, and anoikis resistance. LincRNA-p21 was identified as a crucial mediator in this process, helping sesamin reduce STAT3 activity. Co-administration of a PARP inhibitor with sesamin further enhanced the sensitivity of BC cells to conventional chemotherapeutic drugs (cisplatin, doxorubicin, epirubicin, mitomycin-c), suggesting its potential as an adjuvant therapy. These findings highlight the potential of sesamin as a therapeutic agent, both as a standalone treatment and in combination with conventional chemotherapy, to reduce tumor progression and chemotherapy-related toxicity in BC patients.

## Linked entities

- **Genes:** TP53COR1 (tumor protein p53 pathway corepressor 1) [NCBI Gene 102800311], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774], MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313]
- **Chemicals:** sesamin (PubChem CID 5204), cisplatin (PubChem CID 5460033), doxorubicin (PubChem CID 31703), epirubicin (PubChem CID 41867), mitomycin-c (PubChem CID 5746)
- **Diseases:** bladder cancer (MONDO:0004986)

## Full-text entities

- **Genes:** H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}
- **Diseases:** BC (MESH:D001749), metastasis (MESH:D009362), cancers (MESH:D009369), toxicity (MESH:D064420)
- **Chemicals:** lignan (MESH:D017705), Sesamin (MESH:C054125), sesame oil (MESH:D012715), epirubicin (MESH:D015251), mitomycin-c (MESH:D016685), doxorubicin (MESH:D004317), cisplatin (MESH:D002945)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12035904/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12035904/full.md

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Source: https://tomesphere.com/paper/PMC12035904