title: Baicalin attenuates DDP (cisplatin) resistance in lung cancer by downregulating MARK2 and p-Akt.
abstract: DDP (cisplatin) resistance in lung cancer has been widely reported. Baicalin is a flavone glycoside found in genus Scutellaria. However, the effects of baicalin on DDP resistance in lung cancer are unclear. The aim of present study was to investigate effects of combination of baicalin and DDP on proliferation and invasion of human lung cancer cells, and explore possible mechanisms. MTT assay was utilized to evaluate effects of baicalin and DDP on the proliferation of A549 and A549/DPP (DPP-resistant) human lung cancer cells. The probability sum method was used to determine effects of the drug combination. Transwell invasion assay was utilized to detect tumor cell invasion. The mRNA expression of MARK2 in A549 and A549/DPP cells was detected by qPCR. Protein expression of MARK2, p-Akt and Akt was detected by western blot analysis. Baicalin and DPP when used alone inhibited the proliferation of A549 and A549/DDP cells in a dose-dependent manner at 24 and 48 h. For A549 cells, baicalin (8 µg/ml) antagonized DDP (1, 2, 4 and 8 µg/ml) at 24 h. For A549/DDP cells, baicalin and DDP were additive when the concentration of DDP was 4 µg/ml at 24 h. Effects of baicalin and DDP on proliferation inhibition were additive and synergistic when concentrations of DDP were 8 and 4 µg/ml, respectively, at 48 h for both A549 and A549/DDP cells. When baicalin (8 µg/ml) and DDP (4 µg/ml) were combined, the inhibitory rate of tumor cell invasion increased markedly compared to DPP or baicalin alone groups in both A549 and A549/DDP cells. A549/DDP cells had significantly higher MARK2 mRNA levels and protein expression of MARK2 and p-Akt. Baicalin decreased MARK2 mRNA and protein expression of MARK2 and p-Akt in A549/DDP cells dose-dependently. In conclusion, baicalin and DDP were synergistic at inhibiting proliferation and invasion of human lung cancer cells at appropriate dosages and incubation time in the presence or absence of DDP resistance. The attenuation of DDP resistance was associated with downregulation of MARK2 and p-Akt.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Intensive Care Unit, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005419:Flavonoids / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005419:Flavonoids; C038044:baicalin; C094670:MARK2 protein, human; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin