Evidence map›Paper›PMID 40670295›Full record

ArticleCell proliferation2026

Reversal of MPPa-PDT Resistance in Osteosarcoma by Targeting ROCK2-Mediated Autophagy.

Xuan Yi, Xueqiang Deng, Jianyong Deng, Chen Li, Hong Peng, Yunyan Du, Qing Li, Xiaohua Yan, Xin Hu, Yan Zheng and 5 more

Abstract read
In one paragraph

Article in Cell proliferation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Xuan YiDepartment of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.ORCID https://orcid.org/0000-0002-7701-8888
Xueqiang DengDepartment of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.ORCID https://orcid.org/0000-0003-0003-7092
Jianyong DengDepartment of Vascular & Interventional & Lymphatic Surgery, The First Hospital of Nanchang, Nanchang, China.
Chen LiDepartment of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Hong PengDepartment of Anorectal Surgery, Changcheng Hospital Affiliated to Nanchang University, Nanchang, China.
Yunyan DuDepartment of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China.
Qing LiDepartment of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Xiaohua YanThe MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China.ORCID https://orcid.org/0000-0002-7528-5771
Xin HuDepartment of Orthopedics, Pingxiang People's Hospital, PingXiang, China.
Yan ZhengDepartment of Medical Genetics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Shenliang ChenDepartment of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Ting XiongDepartment of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Debin XuDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Leifeng ChenDepartment of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Liang HaoDepartment of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Funding

Education Department of Jiangxi Province GJJ160251Jiangxi Provincial Department of Science and Technology 20224ACB216001Jiangxi Provincial Department of Science and Technology 20232ACB206033Jiangxi Provincial Department of Science and Technology 20232BCJ22007Jiangxi Provincial Department of Science and Technology 20242BAB23082National Natural Science Foundation of China 82060492National Natural Science Foundation of China 82160539National Natural Science Foundation of China 82203493National Natural Science Foundation of China 82260497National Natural Science Foundation of China 82360565National Natural Science Foundation of China 82360581The Ganpo Talent Program-Innovative Leadership Talent Project gpyc20240196The Medical Engineering Cross Innovation Foundation of Nanchang University 2024JC001
6 · The paper itself

Abstract

Osteosarcoma (OS) is a primary bone tumour that occurs mostly in adolescents and is associated with a high degree of malignancy, early metastasis, and poor prognosis. Pyropheophorbide-a methyl ester-Photodynamic therapy (MPPa-PDT) is a new approach for the clinical treatment of osteosarcoma that develops after surgery and radiotherapy; however, the presence of MPPa-PDT resistance in osteosarcoma greatly limits its efficacy. In this study, we found that Rho-associated coiled-coil containing protein kinase 2 (ROCK2) expression increased in osteosarcoma cells after MPPa-PDT treatment. ROCK2 inhibition results in osteosarcoma sensitivity to MPPa-PDT and is accompanied by a decrease in cellular autophagy levels. Rescue experiments further showed that ROCK2 mediates MPPa-PDT resistance in osteosarcoma by regulating autophagy. Mechanistic studies have shown that ROCK2 mediates autophagy in osteosarcoma cells by regulating the Hippo signalling pathway. ROCK2 overexpression resulted in increased levels of the ROCK2-Salvador homology 1 (SAV1) complex and decreased levels of the mammalian STE20-like protein kinase 1 (MST1)-SAV1 complex, thereby inhibiting activation of the Hippo pathway, which in turn led to osteosarcoma MPPa-PDT resistance by regulating cellular autophagy. ROCK2 competes with MST1 for binding to the aa 28-198 region of SAV1. We also confirmed from a clinical perspective that ROCK2 is an independent prognostic factor in patients with osteosarcoma, is associated with worse patient prognosis, and correlates with the Hippo pathway. Targeted inhibition of ROCK2 by screening for J059-0149 increases the sensitivity of osteosarcoma to MPPa-PDT. In conclusion, our study establishes a novel mechanism to reverse MPPa-PDT resistance in osteosarcoma by targeting ROCK2-mediated autophagy, providing new targets and research ideas for the clinical treatment of osteosarcoma MPPa-PDT resistance.

Indexed as

AutophagyBone NeoplasmsDrug Resistance, NeoplasmOsteosarcomaPhotochemotherapyrho-Associated KinasesAnimalsCell Line, TumorHumansSignal Transductionrho-Associated KinasesROCK2 protein, humanautophagyhippo pathwayMPPa‐PDTosteosarcomaROCK2

Identifiers

PMID40670295
PMCPMC13052181

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.