Traditional Chinese medicine <em>Astragalus </em>polysaccharide enhanced antitumor effects of the angiogenesis inhibitor apatinib in pancreatic cancer cells on proliferation, invasiveness, and apoptosis
Authors: Teng Li
Jun Wu
Wei Ding
Bangwei Cao
Junxian Yu
Qiang Su
Jing Wang
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: AKT; ERK; anti-angiogenesis drug; basic medical research; digestive tumor
Affiliations: Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.

Abstract:  Background: Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Materials and methods: Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting. Cell proliferation was measured by MTS, and migration and invasion were detected by wound-healing and Transwell assays, respectively. Cell apoptosis rate was determined by flow cytometry and cellular autophagy level affected by apatinib, and APS was analyzed by Western blotting. Results: Human pancreatic cancer cell lines ASPC-1 and PANC-1 expressed VEGFR-2, but VEGFR-2 was not detected in SW1990. Either apatinib or APS inhibited cell proliferation in a dose-dependent manner in ASPC-1 and PANC-1. APS in combination with apatinib showed enhanced inhibitory effects on cell migration and invasion compared with apatinib monotherapy in ASPC-1 and PANC-1. Meanwhile, APS combined with apatinib strongly increased cell apoptosis percentage. Western blotting showed that the combination of APS and apatinib significantly enhanced the downregulation of phosphorylated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) (p-AKT and p-ERK) as well as matrix metalloproteinases-9 (MMP-9) expression. In addition, both apatinib and APS induced cellular autophagy. However, the expression of autophagy-related proteins was not further elevated in the combination group. Conclusion: The study first demonstrated that apatinib showed potentially inhibitory effects in pancreatic cancer cells and that APS enhanced the antitumor effects of apatinib through further downregulating the expression of phosphorylation of AKT and ERK as well as MMP-9. 

Retracted: No

PubPeer comments:
 Figure 2A appears to have two sets of repeated images, identified below in red and blue. *** Enhanced brightness ![file] *** Original ![file] , 
 Also, Figure 3A appears to have two images which overlap. These errors are sometimes seem in paper mill or  outsourced papers. *** ![file] , 
 December 24, 2021 Wu J, Wang J, Su Q, et al. Onco Targets Ther. 2018;11:2685u20132698. The authors have advised the incorrect images were inadvertently selected for Figure 2A, on page 2690, due to the dark background and relatively low resolution of photos captured for the wound healing assay. For Figure 3A on page 2691, all Transwell images were captured and saved in one folder labelled by experimental date. Two overlapping images from different visual fields were captured from one well but labelled incorrectly and inadvertently selected for Figure 3A. The correct Figures 2 and 3 are shown in [Download Article] . The authors apologize for these errors and advise they do not affect the results of the paper. ,