Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines

Abstract

Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.

CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement

“…Interestingly, doxycycline, an antibiotic analogue of tetracycline, reduced CD147 levels in a gallbladder carcinoma cell line [19] and gingival crevicular fluid (soluble form) in patients with chronic periodontitis [20]. In addition, monocytes and peripheral blood mononuclear cells treated with azithromycin expressed less MMP-9 [21,22], as well as airways of lung transplant patients did upon treatment with azithromycin [23].…”

“…On March 31, 2020, over 826,000 coronavirus cases, including 40,708 deaths, have already been confirmed around the world, more specifically in 179 countries [1]. These expressive numbers of confirmed cases and death rates call for an urgent demand of effective and available drugs for COVID- 19 treatment.…”

Immunohistochemical Basigin Expression Level in Thyroid Cancer Tissues

“…Another study also found that doxycycline inhibited the proliferation of gallbladder cancer cells by down-regulating the expression levels of BSG and induced an early apoptosis response in cancer cells [64]. In addition, Wang et al [65] found that Metuzumab could inhibit metastasis of esophageal cancer via blocking the function of BSG.…”

Doxycycline Reduces Scar Thickness and Improves Collagen Architecture

“…There are several reports which indicate that doxycycline may act as a collagenase inhibitor. [32][33][34] This was not examined within this study but may ultimately explain the mechanism of reduced skin scarring with local doxycycline treatment. Specifically, collagenases are known to be excreted by fibroblasts and local inflammatory cells.…”