Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by Gcell cycle arrested.

Li LU; Li-Ning YANG; Xue-Xi WANG; Chun-Li SONG; Hong QIN; Yong-Jie WU

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Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by Gcell cycle arrested.

Author: Li LU ¹ ; Li-Ning YANG ¹ ; Xue-Xi WANG ² ; Chun-Li SONG ¹ ; Hong QIN ¹ ; Yong-Jie WU ¹
Author Information

1. Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, 730000, China.
2. Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou, 730000, China. wangxuexi@lzu.edu.cn.
Publication Type:Journal Article
Keywords: ampelopsin; carboplatin; cytotoxic effect; human non-small cell lung cancer; p21
MeSH: Antineoplastic Combined Chemotherapy Protocols; pharmacology; Carboplatin; administration & dosage; pharmacology; Carcinoma, Non-Small-Cell Lung; drug therapy; pathology; Cell Cycle; drug effects; Cell Line, Tumor; Cell Proliferation; drug effects; Drug Synergism; Flavonoids; administration & dosage; pharmacology; Humans; Lung Neoplasms; drug therapy; pathology
From: Chinese journal of integrative medicine 2017;23(2):125-131
CountryChina
Language:English
Abstract:
OBJECTIVETo 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.
METHODSCytotoxic 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.
RESULTSAmp-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 Garrested which mainlym ediated by p 21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway.
CONCLUSIONSAmp-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.