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Original Research

Antiglioma effects of cytarabine on leptomeningeal metastasis of high-grade glioma by targeting the PI3K/Akt/mTOR pathway

, , , , , , , , & show all
Pages 1905-1915 | Published online: 26 Jun 2017

Figures & data

Figure 1 Patient characteristics, treatment, and effect. (A) Changes of magnetic resonance imaging (MRI) appearance, before (left panel) and after (right panel) intrathecal cytarabine treatment, were compared. Tumor lesions in C3–C6 and meninges (white arrows) were partly eliminated in most regions after intrathecal cytarabine chemotherapy according to the radiographic assessment. (B) Values of cerebrospinal fluid (CSF) protein dropped to normal gradually with intrathecal cytarabine therapy from December 2013 to August 2014.

Figure 1 Patient characteristics, treatment, and effect. (A) Changes of magnetic resonance imaging (MRI) appearance, before (left panel) and after (right panel) intrathecal cytarabine treatment, were compared. Tumor lesions in C3–C6 and meninges (white arrows) were partly eliminated in most regions after intrathecal cytarabine chemotherapy according to the radiographic assessment. (B) Values of cerebrospinal fluid (CSF) protein dropped to normal gradually with intrathecal cytarabine therapy from December 2013 to August 2014.

Figure 2 Cytarabine and PI3K/Akt/mTOR pathway inhibitors could inhibit growth of human malignant glioma cells. (A) U87 cells grown in 96-well trays were treated with cytarabine for 72 and 96 h. Cell viability was detected using the MTT assay. (B) Both cytarabine and LY294002 and rapamycin decreased cell viability. (C) and (D) U87 cells were observed with the number of colonies formed. (E) and (F) Cytarabine induced cell apoptosis in a dose-dependent manner. *P<0.05; **P<0.01.

Figure 2 Cytarabine and PI3K/Akt/mTOR pathway inhibitors could inhibit growth of human malignant glioma cells. (A) U87 cells grown in 96-well trays were treated with cytarabine for 72 and 96 h. Cell viability was detected using the MTT assay. (B) Both cytarabine and LY294002 and rapamycin decreased cell viability. (C) and (D) U87 cells were observed with the number of colonies formed. (E) and (F) Cytarabine induced cell apoptosis in a dose-dependent manner. *P<0.05; **P<0.01.
Figure 2 Cytarabine and PI3K/Akt/mTOR pathway inhibitors could inhibit growth of human malignant glioma cells. (A) U87 cells grown in 96-well trays were treated with cytarabine for 72 and 96 h. Cell viability was detected using the MTT assay. (B) Both cytarabine and LY294002 and rapamycin decreased cell viability. (C) and (D) U87 cells were observed with the number of colonies formed. (E) and (F) Cytarabine induced cell apoptosis in a dose-dependent manner. *P<0.05; **P<0.01.

Figure 3 Cytarabine could downregulate the PI3K/Akt/mTOR pathway in human malignant glioma cells. (A) and (B) U87 cells were treated with cytarabine at the indicated doses for 30 min. Protein expression was determined by Western blot assay. Cytarabine inhibits the pI3K/Akt/mTOR/p70S6K signaling pathway in U87 cells. *P<0.05; **P<0.01.

Figure 3 Cytarabine could downregulate the PI3K/Akt/mTOR pathway in human malignant glioma cells. (A) and (B) U87 cells were treated with cytarabine at the indicated doses for 30 min. Protein expression was determined by Western blot assay. Cytarabine inhibits the pI3K/Akt/mTOR/p70S6K signaling pathway in U87 cells. *P<0.05; **P<0.01.

Figure 4 Cytarabine could downregulate antiapoptotic molecules BCL2 and 4-1BB and upregulate the proapoptotic molecule Bax. (A) The mRNA expression of BCL2, Bax, and 4-1BB were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). (B) To delineate the mechanisms underlying the antitumoral properties of cytarabine in malignant glioma. *P<0.05; **P<0.01.

Figure 4 Cytarabine could downregulate antiapoptotic molecules BCL2 and 4-1BB and upregulate the proapoptotic molecule Bax. (A) The mRNA expression of BCL2, Bax, and 4-1BB were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). (B) To delineate the mechanisms underlying the antitumoral properties of cytarabine in malignant glioma. *P<0.05; **P<0.01.

Figure 5 Cytarabine inhibits tumor growth and reduces tumor volume in vivo. (A) and (C) The comparison of relative tumor volume in three groups after two cycles of cytarabine (60 mg/kg) treatment. (B) The growth of tumors was monitored in terms of tumor volume every 2–3 days. (D) and (E) Immunohistochemical (IHC) stainings of Ki-67, cleaved caspase-3, and p-Akt in untreated and cytarabine-treated U87 xenografts. *P<0.05.

Figure 5 Cytarabine inhibits tumor growth and reduces tumor volume in vivo. (A) and (C) The comparison of relative tumor volume in three groups after two cycles of cytarabine (60 mg/kg) treatment. (B) The growth of tumors was monitored in terms of tumor volume every 2–3 days. (D) and (E) Immunohistochemical (IHC) stainings of Ki-67, cleaved caspase-3, and p-Akt in untreated and cytarabine-treated U87 xenografts. *P<0.05.