Evidence map›Paper›PMID 32608202›Full record

ArticleYonsei medical journal2020

Synergistic Antitumor Effects of Combined Treatment with HSP90 Inhibitor and PI3K/mTOR Dual Inhibitor in Cisplatin-Resistant Human Bladder Cancer Cells.

Hyung Joon Kim, Mi Kyung Gong, Cheol Yong Yoon, Jaeku Kang, Mijin Yun, Nam Hoon Cho, Sun Young Rha, Young Deuk Choi

Open access · goldAbstract read
In one paragraph

Article in Yonsei medical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
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

7 citing papers in PubMed, 23 citations in OpenAlex.

  1. HSP90β as a potential prognostic biomarker in urothelial carcinoma: insights from NF-κB, IL-8, and heat-shock protein expression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. 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

8 authors at 2 institutions in 1 country.

Hyung Joon KimDepartment of Urology, Myunggok Medical Research Institute, Konyang University College of Medicine, Daejeon, Korea.ORCID https://orcid.org/0000-0003-3975-3045
Mi Kyung GongSchool of Dentistry, Pusan National University, Yangsan, Korea.ORCID https://orcid.org/0000-0002-9891-8711
Cheol Yong YoonDepartment of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.ORCID https://orcid.org/0000-0002-2845-742X
Jaeku KangDepartment of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.ORCID https://orcid.org/0000-0002-8660-7940
Mijin YunDepartment of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Korea.ORCID https://orcid.org/0000-0002-1712-163X
Nam Hoon ChoDepartment of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Korea.ORCID https://orcid.org/0000-0002-0045-6441
Sun Young RhaDepartment of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Korea.ORCID https://orcid.org/0000-0002-2512-4531
Young Deuk ChoiDepartment of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Korea.ORCID https://orcid.org/0000-0002-8545-5797
Yonsei University · KRKonyang University · KR

Funding

National Research Foundation of Korea 2012R1A1A2043965
6 · The paper itself

Abstract

purposeThe current study aimed to investigate the synergistic antitumor effect of combined treatment with 17-DMAG (HSP90 inhibitor) and NVP-BEZ235 (PI3K/mTOR dual inhibitor) on cisplatin-resistant human bladder cancer cells. MATERIALS AND

methodsHuman bladder cancer cells exhibiting cisplatin resistance (T24R2) were exposed to escalating doses of 17-DMAG (2.5-20 nM) with or without NVP-BEZ236 (0.5-4 μM) in combination with cisplatin. Antitumor effects were assessed by CCK-8 analysis. Based on the dose-response study, synergistic interactions between the two regimens were evaluated using clonogenic assay and combination index values. Flow cytometry and Western blot were conducted to analyze mechanisms of synergism.

resultsDose- and time-dependent antitumor effects for 17-DMAG were observed in both cisplatin-sensitive (T24) and cisplatin-resistant cells (T24R2). The antitumor effect of NVP-BEZ235, however, was found to be self-limiting. The combination of 17-DMAG and NVP-BEZ235 in a 1:200 fixed ratio showed a significant antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range, and clonogenic assay showed compatible results with synergy tests. Three-dimensional analysis revealed strong synergy between the two drugs with a synergy volume of 201.84 μM/mL²%. The combination therapy resulted in G1-phase cell cycle arrest and caspase-dependent apoptosis confirmed by the Western blot.

conclusionHSP90 inhibitor monotherapy and in combination with the PI3K/mTOR survival pathway inhibitor NVP-BEZ235 shows a synergistic antitumor effect in cisplatin-resistant bladder cancers, eliciting cell cycle arrest at the G1 phase and induction of caspase-dependent apoptotic pathway.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzoquinonesCell Cycle CheckpointsCell Line, TumorCisplatinDNA DamageHumansImidazolesLactams, MacrocyclicPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolines17-(dimethylaminoethylamino)-17-demethoxygeldanamycinAntineoplastic AgentsBenzoquinonesCisplatindactolisibImidazolesLactams, MacrocyclicMTOR protein, humanPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesTOR Serine-Threonine Kinases17-DMAGBladder cancerCisplatinNVP-BEZ235

Identifiers

PMID32608202
PMCPMC7329736
OpenAlexW3039226949

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.