ArticleCancer biology & therapy2014
Increasing cisplatin sensitivity by schedule-dependent inhibition of AKT and Chk1.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Osteosarcoma as a communication-driven disease: redefining tumor-bone signaling networks as therapeutic targets.Frontiers in oncology · 2026Review
- Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma.Bone research · 2025Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Selected using bioinformatics and molecular docking analyses, PHA-793887 is effective against osteosarcoma.Aging · 2021Article
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Article
- Checkpoint kinase inhibitor AZD7762 enhance cisplatin-induced apoptosis in osteosarcoma cells.Cancer cell international · 2019Article
- Involvement of Akt in mitomycin C and its analog triggered cytotoxicity in MCF-7 and K562 cancer cells.Chemical biology & drug design · 2018Article
- Synthesis and biological evaluation of 3-(1,3,4-oxadiazol-2-yl)-1,8-naphthyridin-4(1MedChemComm · 2018Article
- RNF138 confers cisplatin resistance in gastric cancer cells via activating Chk1 signaling pathway.Cancer biology & therapy · 2018Article
- Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells.Neoplasia (New York, N.Y.) · 2017Article
- Inhibitory effects of low-intensity pulsed ultrasound sonication on the proliferation of osteosarcoma cells.Oncology letters · 2017Article
- Activation of Akt characterizes estrogen receptor positive human breast cancers which respond to anthracyclines.Oncotarget · 2017Article
- The allosteric AKT inhibitor MK2206 shows a synergistic interaction with chemotherapy and radiotherapy in glioblastoma spheroid cultures.BMC cancer · 2017Article
- The IGF-1R/AKT pathway determines cell fate in response to p53.Translational cancer research · 2016Article
- TIMP3 regulates osteosarcoma cell migration, invasion, and chemotherapeutic resistances.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Tectorigenin inhibits osteosarcoma cell migration through downregulation of matrix metalloproteinases in vitro.Anti-cancer drugs · 2016Article
- Article
- Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells.Biomedical reports · 2016Article
- Targeting protein kinases to reverse multidrug resistance in sarcoma.Cancer treatment reviews · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The effectiveness of DNA damaging chemotherapy drugs can be limited by activation of survival signaling pathways and cell cycle checkpoints that allow DNA repair. Targeting survival pathways and inhibiting cell cycle checkpoints may increase chemotherapy-induced cancer cell killing. AKT and Chk1 are survival and cell cycle checkpoint kinases, respectively, that can be activated by DNA damage. Cisplatin (CP) is a standard chemotherapy agent for osteosarcoma (OS). CP induced apoptosis to varying extents and activated AKT and Chk1 in multiple p53 wild-type and p53-null OS cell lines. A Chk1 inhibitor increased CP-induced apoptosis in all OS cell lines regardless of p53 status. In contrast, an AKT inhibitor increased CP-induced apoptosis only in p53 wild-type OS cells, but not p53 nulll cells. The increased apoptosis in p53 wild-type cells was coincident with decreased p53 protein levels, but increased expression of p53-responsive apoptotic genes Noxa and PUMA. Further studies revealed the inability of AKT inhibitor to CP-sensitize p53-null OS cells resulted from 2 things: 1) AKT inhibition stabilized/maintained p27 levels in CP-treated cells, which then mediated a protective G1-phase cell cycle arrest, 2) AKT inhibition increased the levels of activated Chk1. Finally, schedule dependent inhibition of AKT and Chk1 evaded the protective G1 arrest mediated by p27 and maximized CP-induced OS cell killing. These data demonstrate AKT and Chk1 activation promote survival in CP-treated OS cells, and that strategic, scheduled targeting of AKT and Chk1 can maximize OS cell killing by CP.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.