Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1cell cycle arrested.
OBJECTIVE
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.


METHODS
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.


RESULTS
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 G1arrested which mainlym ediated by p 21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway.


CONCLUSIONS
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.
Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, 730000, China.
Li
L
Lu
Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, 730000, China.|Department of Pharmacy, The Second Hospital of Gansu Province, Lanzhou, 730000, China.
Li-Ning
LN
Yang
Institute of Integrative Traditional and Western Medicine, School of Medicine, Lanzhou University, Lanzhou, 730000, China. wangxuexi@lzu.edu.cn.
Xue-Xi
XX
Wang
Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, 730000, China.
Chun-Li
CL
Song
Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, 730000, China.
Hong
H
Qin
Department of Pharmacology, School of Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, 730000, China.
Yong-Jie
YJ
Wu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology
D005419:Flavonoids; C106407:ampelopsin; D016190:Carboplatin
ampelopsin; carboplatin; cytotoxic effect; human non-small cell lung cancer; p21