The Role of E-Cadherin/β-Catenin in Hydroxysafflor Yellow A Inhibiting Adhesion, Invasion, Migration and Lung Metastasis of Hepatoma Cells

Abstract

Liver cancer is the second leading cause of cancer death. Due to treatments failures from drug resistance and cancer metastasis, discovering more effective treatments is imperative. As an angiogenesis inhibitor extracted from the Chinese herb-Safflower, hydroxysafflor yellow A (HSYA) inhibits the tumor growth in H22-bearing mice. Poorly differentiated hepatoma cells showed the ability to invade and metastasize, which are dependent on the angiogenesis. Accordingly, we hypothesized that HSYA could inhibit the metastasis of liver cancer cells. We investigated the metastasizing potential of human hepatic carcinoma SMMC-7721 cells treated with HSYA. A pulmonary metastatic model of mouse hepatoma H22 cells was established to evaluate the effect and possible mechanism of HSYA on lung metastasis from liver cancer. The results showed that HSYA inhibited the proliferation, invasion and migration of SMMC-7721 cells and reduced its adhesion to the extracellular matrix (ECM). In H22 mice treated with HSYA, the formation of E-cadherin/β-catenin complex resulted in the activation of peroxisome proliferator-activated receptor γ and inhibition of matrix metalloproteinase-2. As a result, the degradation of ECM was reduced and epithelial-mesenchymal transition was prevented. The present findings indicate that HSYA can prevent pulmonary metastasis in liver cancer, which provides strong evidence for the application of HSYA in treatments.

Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

“…27,28 HSYA can also suppress adhesion, invasion, migration, and lung metastasis of hepatoma cells via the E-cadherin/β-catenin pathway, and inhibit angiogenesis of hepatocellular carcinoma by blocking the ERK/MAPK and NF-κB signaling pathways in H22 tumor-bearing mice. 29,30 These data indicate that HSYA plays a significant inhibitory role in tumors. However, relatively little is known concerning the therapeutic function of HYSA in NSCLC mediated with inflammation.…”

“…Previous studies have reported that HYSA induces human gastric carcinoma BGC‐823 cell apoptosis by activating PPARγ and suppresses angiogenesis in transplanted human gastric adenocarcinoma BGC‐823 tumors in nude mice . HYSA inhibits the angiogenesis of hepatocellular carcinoma by blocking ERK/MAPK and NF‐κB signaling pathways in H22 tumor‐bearing mice and suppresses the adhesion, invasion, migration, and lung metastasis of hepatoma cells . However, the role and underlying mechanisms of HYSA in LPS‐induced A549 and H1299 cells remains unknown.…”

“…27,28 HYSA inhibits the angiogenesis of hepatocellular carcinoma by blocking ERK/MAPK and NF-κB signaling pathways in H22 tumor-bearing mice and suppresses the adhesion, invasion, migration, and lung metastasis of hepatoma cells. 29,30 However, the role and underlying mechanisms of HYSA in LPS-induced A549 and H1299 cells remains unknown. Therefore, this study was designed to explore the role and underlying mechanisms of HYSA in the proliferation, apoptosis, migration, and invasion of A549 and H1299 cells induced by LPS.…”

“…Furthermore, HSYA can induce human gastric carcinoma BGC‐823 cell apoptosis by activating peroxisome proliferator‐activated receptor gamma (PPARγ), and suppress tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC‐823 tumors in nude mice . HSYA can also suppress adhesion, invasion, migration, and lung metastasis of hepatoma cells via the E‐cadherin/β‐catenin pathway, and inhibit angiogenesis of hepatocellular carcinoma by blocking the ERK/MAPK and NF‐κB signaling pathways in H22 tumor‐bearing mice . These data indicate that HSYA plays a significant inhibitory role in tumors.…”

Current surgical management of extrapulmonary oligometastatic non-small cell lung carcinoma

“…In addition, metastatic pathways are classified as lymphatic metastasis, hematologic metastasis, and dropped metastasis [8]. At every stage of metastasis, several numbers of cytokines, chemokines, proteolytic enzymes, metalloproteinases and free radicals play roles [10][11][12][13]. In general, it is known that as the tumor diameter and lymphatic invasion increases, the possibility of metastasis increases.…”