Xiaoai Jiedu Recipe Inhibits Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells by Blocking the P38 Mitogen-Activated Protein Kinase (MAPK) Pathway

Abstract

This work was supported by the Nanjing Medical Science and Technology Development Foundation Background: Lung cancer is the leading cause of cancer deaths in the world. Its major histopathological subtype is non-small cell lung cancer (NSCLC). Xiaoai Jiedu recipe (XJR) is a traditional Chinese medicine formula that can suppress growth and invasion of tumor cells. Here, we assessed the antitumor effect of XJR on NSCLC explored the underlying mechanisms. Material/Methods: Three concentrations of XJR (low, middle, and high) were used to treat A549 cells. Cell Counting Kit-8 and colony formation assay were used to measure proliferation of A549 cells. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. The expression of apoptosis-associated proteins was measured by Western blot analysis. Transwell and scratch wound healing assay were used to assess invasion and migration, respectively, of A549 cells. The expression of p38 MAPK pathway-associated proteins were measured using Western blot analysis. Results: XJR suppressed proliferation and promoted apoptosis of A549 cells, especially in the high-dose group. The expression of Bcl-2 was reduced with increasing expression of Bax, cleaved caspase-3, and cleaved caspase-9. Invasion and migration abilities of A549 cells were inhibited after XJR treatment. XJR treatment decreased the expression levels of phosphorylated p38 (p-p38), pERK , and p-JNK in a dose-dependent manner. Conclusions: The results demonstrated that XJR can inhibit proliferation, invasion, and migration, and induce apoptosis of NSCLC by blocking the p38 MAPK pathway, which shows the potential of XJR as a new treatment of NSCLC.

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“…XJR is composed of 7 different herbal ingredients: Hedyotis diffusa (20 g), Radix pseudostellariae (15 g), Bombyx batryticatus (10 g), Cremastra appendiculata (10 g), Centipede (3 g), Radix ophiopogonis (12 g), and Akebia trifoliata Koidz (12 g). Decoction of XJR (2 g/ mL) was prepared according to the standard method, 8 diluted with saline (v/v, 1:1), and stored at 4°C for later use. Cisplatin was purchased from the Shanghai Yuanye Biotechnology Co., Ltd (Shanghai, China).…”

“…The medicated serum was prepared according to the protocol. 8 Briefly, 24 adult Sprague-Dawley rats (6～8 weeks; 220～250g) were divided into XJR (N = 12) and control (N= 12) groups. The rats were fasted for 12 hours.…”

“…6 Xiaoai Jiedu recipe (XJR), a formula long used by Chinese National Medical Professor Zhou Zhongying, 7 consists of 7 Chinese herbal medicines in a specific proportion: Hedyotis diffusa (20 g), Radix pseudostellariae (15 g), Bombyx batryticatus (10 g), Cremastra appendiculata (10 g), Centipede (3 g), Radix ophiopogonis (12 g), and Akebia trifoliata Koidz (12 g). 8 Researchers have determined that XJR can inhibit the growth and invasion of many tumors. 9 However, due to the insufficiency of research methods and complexity of components of XJR, the exact mechanism of XJR in the treatment of HCC is still unclear, which has affected its clinical application and promotion to a certain extent.…”

Recent Advances in Anti-Metastatic Approaches of Herbal Medicines in 5 Major Cancers: From Traditional Medicine to Modern Drug Discovery

“…Besides, XJR affected the expression of apoptosis-related proteins and decreased the expression of p-p38, p-ERK, and p-JNK. In other words, XJR promoted apoptosis and suppressed proliferation of A549 cells by blocking p38/MAPK pathway [ 60 ]. Zhao et al showed that Xiaoji decoction (XJD) inhibited growth of lung cancer cells by increasing phosphorylation of AMP-activated protein kinase alpha (AMPKα).…”

Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis

“…Chinese herbal medicine Wenxia Changfu formula reverses cell adhesion-mediated drug resistance in lung cancer. Xiaoai Jiedu recipe can inactivate p38 MAPK signaling pathway in NSCLC cells to inhibit its proliferation and metastasis ( 174 ). Recent studies have found that CERS6 has important roles in lung cancer migration and metastasis, which proves that the miR-101-CERS6 pathway can be targeted, with potential benefits provided for affected patients ( 175 ).…”