1 Anti-Tumor Mechanism of Pei's Shengxue Granules

1 Anti-Tumor Mechanism of Pei's Shengxue Granules

In recent years, with the advancement of research on anti-tumor traditional Chinese medicines, not only have many formulas with anti-tumor effects been discovered, but the study of their mechanisms has also deepened gradually, broadly divided into the following categories: cytotoxic anti-tumor effects; induction of tumor cell differentiation; production of cell cycle inhibition or induction of tumor cell apoptosis; regulation of the body's immune system; inhibition of telomerase activity; reversal of multi-drug resistance genes in tumors, etc. Many of these mechanisms are closely related to the regulation of tumor-related genes. In this paper, using P27 and cell apoptosis as observation indicators, we observed the regulatory effect of Pei's Shengxue Granules on the expression of tumor-related genes.

We know that the main molecules regulating the cell cycle are cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs). Among them, CDKIs inhibit CDK activity by binding to cyclins, CDKs, or cyclin-CDK complexes, thereby halting the cell cycle and blocking cell proliferation. Due to the biochemical functions and regulatory mechanisms of CDKIs, they play an important role in critical stages of cell growth. As CDK inhibitors, some CDKIs have been proven to be potential tumor suppressors or anti-cancer genes. The recently discovered p27 gene and its product play an extremely important regulatory role in cell growth, including proliferation, differentiation, and apoptosis. Moreover, abnormal P27 expression has been found in certain tumor tissues and tumor cell lines, suggesting a close relationship between P27 and the occurrence and development of tumors, making it a potential anti-cancer gene.

Cell growth is influenced by cell proliferation and cell death. When cell proliferation is inhibited, there will inevitably be a decrease in cell proliferation and an increase in dead cells. The essence of cell division and proliferation is DNA replication, achieved through the continuous cycling of cells. The cell cycle, however, is finely regulated by intracellular signaling pathways and various factors. In particular, cells in the G0/G1 phase are sensitive to external environmental factors and can be stimulated to accelerate or slow down cell proliferation. When the cell cycle is disrupted, cell proliferation will be inhibited, and impaired DNA synthesis is one of the most common causes of cell cycle disruption.

P27 protein can restrictively regulate the progression of the cell cycle, mainly by inhibiting the function of cyclin-CDK complexes.

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This effect is primarily achieved by inhibiting the activity of cyclin-E-CDK2 and cyclin-D-CDK4 complexes, which are key G1-phase kinase complexes [30]. P27 protein is the main factor in the negative regulatory pathway at the G1/S restriction point of the cell cycle, primarily acting in the G1 phase to inhibit the transition from G1 to S phase, inducing G1-phase arrest and suppressing cell proliferation. P27 protein also plays a crucial role in controlling the G0/G1 phase stagnation of the cell cycle; moreover, P27 protein can promote apoptosis and affect cell differentiation [31]. A decrease in P27 protein expression can promote cell proliferation and malignant transformation, closely related to the occurrence of tumors [32–33].

The results of this experiment show that in the tumor tissue of model-group tumor-bearing mice, the positive expression of P27 protein is abnormally reduced, with few brown-yellow areas visible in immunohistochemical staining. In contrast, the P27 protein expression in the various doses of Pei's Shengxue Granules combined with 5-Fu groups and the 5-Fu group is significantly increased, with statistically significant differences compared with the model group (P<0.05). Furthermore, compared with the 5-Fu group, all doses of Pei's Shengxue Granules combined with 5-Fu show varying degrees of increase. This suggests that Pei's Shengxue Granules can achieve its anti-tumor effect by upregulating P27 protein expression, inhibiting the transition from G1 to S phase, inducing G1-phase arrest, suppressing cell proliferation, and promoting programmed cell death.

In summary, Pei's Shengxue Granules can exert their anti-tumor effect by upregulating P27 protein expression, influencing the cell cycle, inhibiting tumor cell proliferation, and promoting tumor cell apoptosis.

2 Antagonistic and Synergistic Effects of Pei's Shengxue Granules on the Toxic Side Effects Caused by 5-Fu in Tumor-Bearing Mice

Recent studies have shown that the occurrence, development, and prognosis of tumors are closely related to the immune status of the host carrying the tumor. After a tumor develops, the body's own immune function declines, and the number of suppressive cells within the body increases significantly, inhibiting the body's immune response against the tumor and allowing the tumor to evade immune surveillance, thereby promoting tumor growth.

The thymus is the most important central immune organ in the body, serving as the site for the development, differentiation, and maturation of T cells. T cells are important immune cells in the human body, capable of mediating cellular immunity and participating in the execution and regulation of various immune functions, with anti-tumor immunity primarily relying on cellular immunity. Many animal experiments have shown that the thymus of tumor-bearing hosts often shrinks, with reduced weight and a significant decrease in thymic cells. At this point, the body's cellular immune function and related immune capabilities decline, which is detrimental to the body's fight against tumor cells. The spleen is the largest peripheral immune organ in the human body, serving as the residence of various immune cells and the main base for generating immune responses to antigens and producing immune effector substances. Currently, it is believed that the spleen has a dual nature in tumor immunity: in the early stages of tumor development, it exerts a positive immune effect, inhibiting tumor growth. However, in the later stages of tumor growth, the spleen produces a large number of suppressive cells and releases active soluble substances that inhibit the body's immune function.

Currently, surgery and radiotherapy/chemotherapy still dominate clinical cancer treatment. On the one hand, the immune function of tumor-bearing bodies is suppressed; on the other hand, during clinical radiotherapy and chemotherapy, the body suffers further damage. Although radiotherapy and chemotherapy can directly kill tumor cells, they also suppress the function of the hematopoietic system and immune-active cells, leading to symptoms such as decreased white blood cell count and weakened immune function, thereby weakening the body's ability to fight tumors and infections [34].

Traditional Chinese medicine, widely used as an adjuvant to chemotherapy in the prevention and treatment of malignant tumors, has the characteristics of multiple targets and multiple effects, with few toxic side effects. On the one hand, it can enhance the sensitivity of chemotherapy, helping to treat cancer and prevent metastasis and recurrence; on the other hand, it has a holistic regulatory effect on the body, alleviating the toxic side effects caused by chemotherapy. Sensitization refers to cancer patients simultaneously taking traditional Chinese medicine during chemotherapy in order to increase the sensitivity of chemotherapy drugs to tumor treatment and improve therapeutic outcomes. Specifically, sensitization includes two aspects: first, enhancing efficacy—using traditional Chinese medicine to further improve the original efficacy of chemotherapy; second, reducing the dosage of chemotherapy while maintaining effectiveness, or making tumors that were originally insensitive to chemotherapy effective after using traditional Chinese medicine [35]. Traditional Chinese medicine treatment aims to improve the host's constitution, using the method of reinforcing vital energy and consolidating the root to enhance the body's immune function.

The results of this experiment show that Pei's Shengxue Granules have a clear enhancing effect on the decline of thymus and spleen indices caused by 5-Fu, improving the body's immune function, strengthening the body's resistance to harmful external stimuli, and reducing bodily damage. It is evident that Pei's Shengxue Granules can serve as an adjuvant to chemotherapy, alleviating the toxic side effects caused by chemotherapy. In addition, combining Pei's Shengxue Granules with 5-Fu can further inhibit tumor growth and increase the anti-tumor effect of 5-Fu.

In summary, Pei's Shengxue Granules can enhance the body's immune function by increasing thymus and spleen indices, strengthening the body's resistance to external stimuli, thereby counteracting the clinical toxic side effects caused by chemotherapy drugs. Moreover, Pei's Shengxue Granules can work synergistically with chemotherapy drugs to inhibit tumor growth, increase the tumor suppression rate, and better fulfill their role in treating tumors.

Conclusion