Enhanced Anti-Tumor Effect of Zoledronic Acid Combined with Temozolomide against Human Malignant Glioma Cell Expressing O6-Methylguanine DNA Methyltransferase

Fukai, Junya; Koizumi, Fumiaki; Nakao, Naoyuki

doi:10.1371/journal.pone.0104538

Cited by 23 publications

(12 citation statements)

References 29 publications

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“…The mechanisms for anti‐cancer effect of TMZ were very complicated, and had not yet been clear. The mechanisms may include breaking the glioma cells’ DNA [Fukai et al, ] or inhibiting Wnt3a/glycogen synthase‐3 kinase ß‐catenin, TROY, PI3K signaling pathway [Chen et al, ; Wu et al, ]. In present study, our data showed that TMZ had cytotoxic effect on glioma cells, which could significantly inhibit proliferation, affect differentiation of glioma cell by arresting the cell cycle in the G2/M phase.…”

Section: Discussionsupporting

confidence: 53%

Down‐Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide‐Induced Glioma Cells Growth Inhibition and Invasion Impairment

Chen

Gao

Jiang

et al. 2017

J of Cellular Biochemistry

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Glioma is the most common and lethal central nervous system tumors. Temozolomide (TMZ) is an effective drug for malignant glioma, however, the intracellular and molecular mechanisms behind this anti-cancer effect have yet to be fully understood. The aim of the present study was to determine whether TMZ inhibits proliferation, invasion of glioma cells in vitro and whether these effects can be mediated through modulation of aquaporin 4 (AQP4) and phosphorylation of the MAPK pathway. The viability of U87 and U251 human glioma cells was evaluated using MTT assay. The cell cycle distribution was detected with flow cytometry. Migration ability and invasion ability were tested by scratch assays and transwell assays, respectively. The levels of AQP4 and MAPK were measured using immunoblot analyses. Our results showed that TMZ inhibited proliferation, migration and invasion, and induced G2/M arrest in U87 and U251 glioma cell lines. These changes were associated with a decrease in the levels of AQP4 expression as well as activation phosphorylated level of p38. Treatment with a p38 chemical activator (anisomycin) resulted in similar effects as TMZ treatment on glioma cells. And p38 chemical inhibitor (SB203580) could block these effects in glioma treated with TMZ, suggesting a direct up-regulation of the p38 signaling pathway. Therefore, we identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. J. Cell. Biochem. 118: 4905-4913, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 53%

Down‐Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide‐Induced Glioma Cells Growth Inhibition and Invasion Impairment

Chen

Gao

Jiang

et al. 2017

J of Cellular Biochemistry

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“…RT plus concomitant and adjuvant TMZ, an alkylating agent, currently represents the standard of care for newly diagnosed GB patients (9). Consequently, carmustine wafers may be implanted concomitantly with these combined standard treatments.…”

Section: Discussionmentioning

confidence: 99%

Rapid regression of glioblastoma following carmustine wafer implantation: A case report

Fukai¹,

Nishibayashi²,

Uematsu³

et al. 2016

Molecular and Clinical Oncology

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Abstract. Carmustine wafers, which are locally delivered chemotherapy in the form of biodegradable implants, confer a survival benefit to patients with glioblastoma (GB) following surgical resection. While the adverse events of this method, including gas retention and perifocal edema, have been extensively investigated, the immediate efficacy of the implant has rarely been reported. To the best of our knowledge, this is the first reported case of GB in which the tumor rapidly regressed after partial surgical removal followed by implantation of carmustine wafers. A 77-year-old woman presented with motor aphasia and right hemiparesis. Neuroimaging revealed a tumor located in the left frontal lobe of the brain. The tumor was partially removed under 5-aminolevulinic acid fluorescence guidance and 8 carmustine wafers were implanted in the resection cavity. The histopathological findings suggested the diagnosis of GB. Genetic and immunohistochemical analyses revealed O 6 -methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and low MGMT protein expression, respectively, in the tumor cells. One month after the operation, when adjuvant temozolomide chemotherapy was planned, computed tomography and magnetic resonance imaging revealed a marked regression of the residual tumor and perifocal edema. The patient's symptoms and signs had improved. As adjuvant temozolomide without radiation was therapeutically beneficial, the tumor gradually regressed and the patient has remained progression-free for >12 months after the operation. Therefore, adjuvant local chemotherapy with carmustine wafer implants was able to induce rapid regression of GB. IntroductionGlioblastoma (GB), a frequent type of malignant glioma, is the most common primary brain tumor and is associated with a poor prognosis. Despite aggressive multimodality treatments, including cytoreductive surgery, radiotherapy (RT) and systemic chemotherapy, GB recurs and it is invariably fatal. Additional therapeutic strategies are urgently required to elicit prolong tumor control and patient survival (1).A carmustine (bis-chloroethylnitrosourea, BCNU; an alkylating agent of the nitrosourea family) wafer (Gliadel ® ; Eisai Inc., Tokyo, Japan) is a controlled-release preparation of BCNU that is implanted into the brain (2). Carmustine wafers, lined along the wall of the resection cavity following tumor removal, exert antitumor effects on the residual tumor as adjuvant local chemotherapy. This implant has been shown to enhance the overall survival of patients with malignant gliomas in controlled clinical trials in the United States and Europe (3). A prospective, multicenter phase-I/II study on Japanese patients was recently performed and the application of carmustine wafers has been covered by Japanese public health insurance since 2012 (2).Through local application, an increased concentration of carmustine may be delivered to the tumor bed over a period of ≥3 weeks, during which, local reactions caused by this chemotherapeutic may occur (4). Previous studies hav...

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“…It is well known that glioma cells have significant proliferation ability and a low apoptosis rate, as well as a powerful resistance to chemotherapy, radiation and biological treatment (13)(14)(15). These characteristics contribute to the malignant growth of tumors and may be a key reason for the recurrence of glioma (16).…”

Section: Discussionmentioning

confidence: 99%

miR-128 regulates the apoptosis and proliferation of glioma cells by targeting RhoE

et al. 2015

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Abstract. In this study, we investigate whether miR-128 is capable of regulating the apoptosis and proliferation of human U251 glioma cells by downregulating RhoE. The expression of miR-128 was assessed by quantitative polymerase chain reaction in normal brain tissue and glioma samples. A significant downregulation of the expression of miR-128 was detected in glioma in contrast to normal brain tissue. Following the transfection of pre-miR-128 and anti-miR-128 into U251 cells, the high expression of miR-128 could inhibit proliferation and induce apoptosis in U251 cells, and those effects could be restored by miR-128 knockdown. To analyze the regulation mechanism of miR-128, TargetScan, miRanda and PicTar were used to ascertain whether RhoE was a potential target gene. Next, luciferase activity assay and western blot analysis confirmed that RhoE was a direct and specific target gene of miR-128. The advanced effects of pre-miR-128 on the apoptosis and proliferation of U251 cells were reversed by the upregulation of RhoE expression. In summary, aberrantly expressed miR-128 regulates apoptosis and proliferation in human glioma U251 cells partly by directly targeting RhoE. This finding may offer a new potential therapeutic strategy for the treatment of glioma.

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Enhanced Anti-Tumor Effect of Zoledronic Acid Combined with Temozolomide against Human Malignant Glioma Cell Expressing O6-Methylguanine DNA Methyltransferase

Cited by 23 publications

References 29 publications

Down‐Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide‐Induced Glioma Cells Growth Inhibition and Invasion Impairment

Down‐Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide‐Induced Glioma Cells Growth Inhibition and Invasion Impairment

Rapid regression of glioblastoma following carmustine wafer implantation: A case report

miR-128 regulates the apoptosis and proliferation of glioma cells by targeting RhoE

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