1.3.2 Bcl-2

1.3.2 Bcl-2

Bcl-2, or B-cell lymphoma/leukemia-2 proto-oncogene, was first discovered in mouse B-cell lymphoma by Tsujimoto et al. in 1985 [4], and is an important member of the Bcl-2 gene family. This gene is located at 18q21 and its molecular structure consists of three exons (the first one lacks translation function, while the second and third have clear coding functions as protein-coding regions) and one intron. The Bcl-2 encoded protein has a molecular weight of 26 kDa and is composed of 229 amino acid residues. It is a membrane-associated protein, and studies have confirmed its presence in the inner mitochondrial membrane, nucleus, and endoplasmic reticulum membrane.

Under certain physiological or pathological conditions, cells undergo a genetically regulated, orderly process of self-destruction known as apoptosis. Bcl-2 promotes cell growth by blocking the programmed cell death or apoptosis process [4], thereby disrupting the homeostatic balance of cells. Damaged or mutated cells cannot be eliminated in time and, under the combined action of proliferative genes and growth-suppressing genes, eventually develop into tumors.

The mechanisms by which Bcl-2 inhibits apoptosis may include [47]: exerting its regulatory function on apoptosis through self-dimerization or formation of heterodimers with proteins such as Bax; interfering with the release of Ca²⁺ from the endoplasmic reticulum in apoptotic cells to exert anti-apoptotic effects; directly or indirectly affecting apoptosis through interactions with cellular signaling proteins; and inhibiting apoptosis or preventing free radical production through antioxidant activity. Abnormal overexpression of Bcl-2 has been found in various tumor tissues and is closely related to tumor occurrence and development. The expression of Bcl-2 in hepatocellular carcinoma tissue remains unclear [49], but most believe that the positive expression rate of Bcl-2 protein in hepatocellular carcinoma tissue is significantly higher than in normal liver tissue. Zeppa et al. [50] examined Bcl-2 expression in 16 cases of hepatocellular carcinoma tissue, finding a Bcl-2 expression rate as high as 19%, with 14 cases being well-differentiated. Bcl-2 expression is correlated with the degree of differentiation of hepatocellular carcinoma cells. Zong Lei et al. [51] observed the dynamic expression of Bcl-2 during the process of hepatocellular carcinogenesis and found that Bcl-2 expression in the cancer group was significantly higher than in the transformed group and the normal control group. As the histological morphology of liver tissue changed, the level of Bcl-2 expression in hepatocyte cytoplasm showed an increasing trend.

2 Understanding of Liver Cancer in Traditional Chinese Medicine