Cisplatin is a chemotherapy drug often used to treat advanced gastric cancer. However, gastric cancer cells can develop a resistance to this drug, causing treatment to fail. In a new study published in the Chinese Journal of Natural Medicines, researchers from Shanghai University of Traditional Chinese Medicine evaluated the potential of an herbal formula known for its anti-cancer activities. They found that zuo jin wan (ZJW) can aid in cancer treatment by helping restore the sensitivity of otherwise resistant gastric cancer cells to cisplatin.
The traditional Chinese medicine (TCM) formula zuo jin wan is composed of the rhizome of Coptis chinensis (Chinese goldthread) and the fruits of Evodia rutaecarpa (evodia) in a 6:1 ratio. According to studies, C. chinensis, the main component of ZJW, has the ability to reverse multi-drug resistance (MDR) in cancer cells. Meanwhile, E. rutaecarpa, also known as Tetradium ruticarpum, can induce apotosis in some cancer cells, such human melanoma cells, hepatocellular carcinoma cells and human colorectal carcinoma cells.
In TCM, ZJW is used to treat stomach-related conditions, such as acute and chronic gastritis, peptic ulcer, indigestion, esophageal reflux and gastralgia, among others. It is also used to address fever, hypertension, hepatitis, allergic colitis and Helicobacter pylori infection. (Related: Honey and black cumin found to treat H. Pylori patients.)
Treatment failure due to chemo-resistance is common in human gastric cancer cases. Hence, scientists are currently searching for potential drugs that can help re-sensitize these cells to treatments like cisplatin.
In the present study, researchers investigated the effects of the traditional Chinese herbal formula ZJW on gastric cancer cells. They also aimed to elucidate the mechanism underlying its anti-cancer activities.
In their previous study, the researchers showed that ZJW can increase mitochondrial apoptosis (programmed cell death) in gastric cancer cells by promoting the translocation of cofilin-1. Cofilin-1 is a protein that plays an important role in the development of MDR by cancer cells. The researchers found that mitochondrial translocation of cofilin-1 subsequently leads to the activation of the mitochondrial apoptosis pathway.
To continue their evaluation of ZJW, the researchers constructed a gastric cancer cell model using samples derived from cancer patients. They used different techniques, such as immunofluorescent staining, Western blot, Cell Counting Kit-8 (CCK-8) and flow cytometry to identify cancer cells, detect protein expression, evaluate cell proliferation and assess cell apoptosis, respectively.
The researchers reported that ZJW inhibited proliferation and induced apoptosis in primary cisplatin-resistant gastric cancer cells. They found that apoptosis was mediated by induction of cofilin-1 mitochondrial translocation, followed by down-regulation of Bcl-2, a regulator of cell death, and up-regulation of Bax, an activator of apoptosis.
The researchers also found that cisplatin-resistant gastric cancer cells had higher levels of the AKT protein than cisplatin-sensitive gastric cancer cells. Activation of AKT, which is important for cell proliferation and survival, could attenuate ZJW-induced sensitivity to cisplatin. Taken together, these results suggest that ZJW can increase the chemosensitivity of cisplatin-resistant primary gastric cancer cells by inducing mitochondrial apoptosis and AKT inactivation.
Based on these findings, the researchers concluded that combining chemotherapy with ZJW is a promising therapeutic strategy for patients with chemo-resistant gastric cancer cells.