The researchers found that triptolide, an extract of Chinese traditional medicine Tripterygium wilfordii, can inhibit GRP78 and eventually lead to the death of pancreatic cancer cells. GRP78, glucose regulated protein 78, is a member of heat shock protein 70 family. As a molecular chaperone, GRP78 plays an important role in protein folding and transport and endoplasmic reticulum stress response. It is highly expressed in a variety of tumor tissues. Inhibiting its expression level or linking GRP78 promoter to suicide gene can be used in tumor therapy.

      Pancreatic cancer is the fourth most common cause of cancer death in the United States. This is a disastrous disease for patients. To some extent, due to the replication of aggressive cells and the growth of tumors, the development rate of pancreatic cancer is surprising, and the survival rate is less than 5 years (less than 5).

      GRP78 is a protein that can protect cell death. The number of GRP78 in cancer cells is much higher than that in normal tissues, and it is considered to play an active role in the growth and development of pancreatic cancer cells. Researchers from the University of Minnesota have found thatTriptolide aIt can effectively inhibit GRP78 and eventually lead to the death of pancreatic cancer cells.

      In mammals, the process of using proteins, called protein folding, must occur in the endoplasmic reticulum. If protein folding is not fast enough, unfolded proteins begin to accumulate and cells become tense. Persistent endoplasmic reticulum stress triggers the unfolded protein response (UPR). At first, UPR can help quickly start the protein folding ability of cells and make them work normally again. However, if this problem cannot be solved well, UPR will trigger apoptosis. GRP78 helps cells survive long enough to correct protein folding problems. However, a larger number of GRP78 in pancreatic cancer cells have activity, which helps cancer cells avoid apoptosis and make them survive and reproduce.

      Previous studies have confirmed that triptolide has a negative effect on the viability of pancreatic cancer cells, preventing their growth and proliferation. In this study, researchers studied the effects of triptolide on human pancreatic cancer cells and tissues. The results showed that UPR worked normally in triptolide treated cells, resulting in cell death. Studies have shown that although the increased expression of GRP78 gives tumor cells a survival advantage, long-term exposure to triptolide induced chronic endoplasmic reticulum stress eventually leads to cell death. Triptolide inhibits GRP78 by activating intracortical stress. Thus, triptolide provides a new mechanism for the medical community to inhibit the growth and survival of pancreatic cancer cells.