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.

Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway

“…Many studies have shown that BA could inhibit the expression of p-Akt in the PI3K/Akt pathway to promote the apoptosis of tumor cells. 22 , 23 , 24 Molecular docking technology predicted that BAD and BAL could bind Akt protein better than BA, especially because BAL had the highest binding ability (total score >4) ( Figure 5 ). To determine whether BAD or BAL promotes apoptosis the as same as BA by inhibiting the expression of p-Akt, western blot analysis was used to detect the expression of total Akt (T-Akt), p-Akt, Bax, Bcl-2, caspase-3, and caspase-9 proteins extracted from A549 cells with different concentrations of BA, BAD, and BAL.…”

“… 22 , 23 For example, Xu et al. 24 found that BA could inhibit the proliferation and migration of A549 and DDP (cisplatin)-resistant A549 by inhibiting the overexpression of phosphorylated (p-)Akt. However, the relatively low antitumor activity of BA is the main factor restricting its application as a new antitumor drug.…”

Circ_0000079 Decoys the RNA-Binding Protein FXR1 to Interrupt Formation of the FXR1/PRCKI Complex and Decline Their Mediated Cell Invasion and Drug Resistance in NSCLC

“…DDP treatment demonstrates favorable outcomes initially, but later cancer cells rapidly obtain DDP resistance leading to relapse and therapeutic failure 4,29 . Drug resistance could be caused by various mechanisms, such as a reduction in intracellular drug concentration, the activation of detoxifying systems, the activation of DNA repair, and the inhibition of apoptosis 30,31 . Recently, more studies have revealed that ERK signaling cascades play a critical role in the transmission of signals from growth factor receptors to prevent apoptosis, and it also proved that ERK signaling cascades may be a critical pathway conferring acquired drug resistance [32][33][34] .…”

Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase

“…Previous studies showed that baicalin inhibited lung cancer cells proliferation and metastasis [22]. Baicalin also can attenuate resistance to chemoradiotherapy of lung cancer [40–41]. Although baicalin is a pleiotropic protein kinase inhibitor, the detailed mechanism of its pharmacological function remains unclear in lung cancer cells.…”