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Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1 cell cycle arrested
- Chinese Journal of Integrative Medicine Vol. 23, Issue 2, Pages: 125-131(2017)
- Affiliations：
1. Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province,Lanzhou,China
2. Department of Pharmacy, The Second Hospital of Gansu Province,Lanzhou,China
3. Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University,Lanzhou,China
- Author bio：
- Funds：Supported by the Natural Science Foundation of Gansu Province, China (No. 0710RJZA044)
DOI：10.1007/s11655-016-2591-1
CLC：Published：2017，
Published Online：14 June 2016，
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Lu, L., Yang, Ln., Wang, Xx. et al. Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1 cell cycle arrested., Chin. J. Integr. Med. 23, 125–131 (2017). https://doi.org/10.1007/s11655-016-2591-1
Li Lu, Li-ning Yang, Xue-xi Wang, et al. Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1 cell cycle arrested. [J]. Chinese Journal of Integrative Medicine 23(2):125-131(2017)
Lu, L., Yang, Ln., Wang, Xx. et al. Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1 cell cycle arrested., Chin. J. Integr. Med. 23, 125–131 (2017). https://doi.org/10.1007/s11655-016-2591-1 DOI：
Li Lu, Li-ning Yang, Xue-xi Wang, et al. Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1 cell cycle arrested. [J]. Chinese Journal of Integrative Medicine 23(2):125-131(2017) DOI： 10.1007/s11655-016-2591-1.
摘要
To evaluate the cytotoxic effects of ampelopsin sodium (Amp-Na) and carboplatin (CBP) used alone or in combination on human non-small cell lung cancer (NSCLC) cells SPC-A1 in vitro and its related mechanism. Cytotoxic effects were assessed by 3-(4
5-dimethylthiazol-2-yl)-2
5-diphenyltetrazolium bromide (MTT) assays. The synergistic effects of the drugs were calculated with coefficient of drug interaction (CDI). Cell cycle was determined by flow cytometry (FCM). The levels of p53
p21
cyclinE
cyclinD1
and phosphorylated cyclin-dependent kinase-2 (p-CDK2) were evaluated by Western blot. Amp-Na (6.25–200 μg/mL) and CBP (3.13–100 μg/mL) alone exhibited prominent cytotoxic activity in a concentration-dependent manner on SPC-A1 cells with 50% inhibitive concentration values of 57.07±14.46 and 34.97±6.30 μg/mL
respectively. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone (P<0.05 or 0.01). The CDI analysis confirmed the synergy of Amp-Na and CBP on inhibiting cancer cell viability across a wide concentration range (CDI <1). FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G1 arrested which mainlym ediated by p 21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. Amp-Na exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. These results suggest that Amp-Na may be applied to enhance the anticancer action of CBP.
Abstract
To evaluate the cytotoxic effects of ampelopsin sodium (Amp-Na) and carboplatin (CBP) used alone or in combination on human non-small cell lung cancer (NSCLC) cells SPC-A1 in vitro and its related mechanism. Cytotoxic effects were assessed by 3-(4
5-dimethylthiazol-2-yl)-2
5-diphenyltetrazolium bromide (MTT) assays. The synergistic effects of the drugs were calculated with coefficient of drug interaction (CDI). Cell cycle was determined by flow cytometry (FCM). The levels of p53
p21
cyclinE
cyclinD1
and phosphorylated cyclin-dependent kinase-2 (p-CDK2) were evaluated by Western blot. Amp-Na (6.25–200 μg/mL) and CBP (3.13–100 μg/mL) alone exhibited prominent cytotoxic activity in a concentration-dependent manner on SPC-A1 cells with 50% inhibitive concentration values of 57.07±14.46 and 34.97±6.30 μg/mL
respectively. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone (P<0.05 or 0.01). The CDI analysis confirmed the synergy of Amp-Na and CBP on inhibiting cancer cell viability across a wide concentration range (CDI <1). FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G1 arrested which mainlym ediated by p 21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. Amp-Na exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. These results suggest that Amp-Na may be applied to enhance the anticancer action of CBP.
关键词
ampelopsincarboplatinhuman non-small cell lung cancercytotoxic effectp21
Keywords
ampelopsincarboplatinhuman non-small cell lung cancercytotoxic effectp21
references
Sone S, Yano S. Molecular pathogenesis and its therapeutic modalities of lung cancer metastasis to bone. Cancer Metastasis Rev 2007;26:685–689.
Zochbauer-Muller S, Gazdar AF, Minna JD. Molecular pathogenesis of lungcancer. Annu Rev Physiol 2002;64:681–708.
Raso MG, Wistuba II. Molecular pathogenesis of earlystage non-small cell lung cancer and a proposal for tissue banking to facilitate identification of new biomarkers. J Thorac Oncol 2007;2:S128–135.
Junker K, Wiethege T, Muller KM. Pathology of small-cell lung cancer. J Cancer Res Clin Oncol 2000; 126:361–368.
Rodon J, Jacobs CD, Chu Q, Rowinsky EK, Lopez-Anaya A, Takimoto CH, et al. A phase I pharmacokinetic study of bexarotene with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol 2012;69:825–834.
Xu Y, Ma S, Ji Y, Sun X, Jiang H, Chen J, et al. Concomitant chemoradiotherapy using pemetrexed and carboplatin for unresectable stage III non-small cell lung cancer (NSCLC): preliminary results of a phase II study. Lung Cancer 2011;72:327–332.
Wang Y, Zhou L, Li R. Determination of ampelopsin in the different parts of Ampelopsis grossedentata in different seasons by RP-HPLC. J Chin Med Mater (Chin) 2002;25:23–24.
He ZF, Liu DY, Zeng S, Ye JT. Study on preparation of ampelopsin liposomes. China J Chin Mater Med (Chin) 2008;33:27–30.
He ZF, Zeng S, Hou JJ, Liu DY. Optimizing the extracting technique of ampelopsin from Ampelopsis cantoniensis Planch by a uniform design method. J Chin Med Mater (Chin) 2006;29:718–720.
Qi S, Xin Y, Guo Y, Diao Y, Kou X, Luo L, Yin Z. Ampel opsin reducesendo to xic inflammation via repressing ROS-mediated activation of PI3K/Akt/NFkappaB signaling pathways. Int Immunopharmacol 2012;12:278–287.
Kou X, Shen K, An Y, Qi S, Dai WX, Yin Z. Ampelopsin inhibits H2O2 -induced apoptosis by ERK and Akt signaling pathways and up-regulation of heme xxygenase-1. Phytother Res 2011;11:231–235.
Ye J, Guan Y, Zeng S, Liu D. Ampelopsin prevents apoptosis induced by H2O2 in MT-4 lymphocytes. Planta Med 2008;74:252–257.
Ruan LP, Yu BY, Fu GM, Zhu DN. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal 2005;38:457–464.
Zhang B, Dong S, Cen X, Wang X, Liu X, Zhang H, et al. Ampelopsin sodium exhibits antitumor effects against bladder carcinoma in orthotopic xenograft models. Anticancer Drugs 2011;60:73–78.
Hao JQ, Li Q, Xu SP, Shen YX, Sun GY. Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro. Chin Med J 2008;121:602–607.
Socinski MA, Saleh MN, Trent DF, Dobbs TW, Zehngebot LM, Levine MA, et al. A randomized, phase II trial of two dose schedules of carboplatin/paclitaxel/cetuximab in stage IIIB/IV non-small-cell lung cancer (NSCLC). Ann Oncol 2009;20:1068–1073.
De Candis D, Stani SC, Bidoli P, Bedini VA, Potepan P, Navarria P, et al. Induction chemotherapy with carboplatin/ paclitaxel followed by surgery or standard radiotherapy and concurrent daily low-dose cisplatin for locally advanced non-small cell lung cancer (NSCLC). Am J Clin Oncol 2003;26:265–269.
Grigorescu AC, Draghici IN, Nitipir C, Gutulescu N, Corlan E. Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine (VLB) in advanced nonsmall-cell lung cancer (NSCLC) stages III and IV: a phase III randomised trial. Lung Cancer 2002;37:9–14.
Adema AD, van der Born K, Honeywell RJ, Peters GJ. Cell cycle effects and increased adduct formation by temozolomide enhance the effect of cytotoxic and targeted agents in lung cancer cell lines. J Chemother 2009;21:338–346.
Esposito V, Baldi A, De Luca A, Tonini G, Vincenzi B, Santini D, et al. Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer. J Clin Pathol 2005;58:734–739.
Esposito V, Baldi A, Tonini G, Vincenzi B, Santini M, Ambrogi V, et al. Analysis of cell cycle regulator proteins in non-small cell lung cancer. J Clin Pathol 2004;57:58–63.
Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 2009;9:400–414.
Wang YL, Luo YL, Chen C, Li NL, She YL, Zhang L. The influence of the total flavonoids of Hedysarum polybotry on the proliferation, cell cycle, and expressions of p21Ras and proliferating cell nuclear antigen gene in erythroleukemia cell line K562. Chin J Integr Med 2012;18:385–390.
Gartel AL, Radhakrishnan SK. Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res 2005;65:3980–3985.
Reinhardt HC, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet 2012;28:128–136.
Dai C, Gu W. p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med 2010;16:528–536.
Hawkins DS, Demers GW, Galloway DA. Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. Cancer Res 1996;56:892–898.
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