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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Bax is involved in the anticancer activity of Velcade in colorectal cancer
Liya Su1, Qimuge Suyila1, Ling Yang1
1Clinical Medical Research Center of The Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
Abstract:
Numerous chemotherapeutic agents promote tumor cell death by activating the intrinsic apoptosis signaling pathway. This pathway is regulated by mitochondrial dysfunction, which occurs through an intricate process controlled by complex interactions between B-cell lymphoma 2 (Bcl-2) family members and other cellular proteins. Bcl-2-associated X protein (Bax) is a proapoptotic protein that is an essential component of the intrinsic apoptosis signaling pathway. Patients lacking Bax may be less sensitive to chemotherapy due to an impaired intrinsic apoptosis signaling pathway. The present study demonstrated that Bax expression in colorectal cancer (CRC) tissues was typically increased compared with that in adjacent normal tissues. Furthermore, Bax-/- HCT-116 cells exhibited reduced proliferation and colony formation ability compared with Bax+/+ HCT116 cells, although the rate of apoptosis of these cells remained unchanged. However, Bax-/- HCT116 cells became more resistant to apoptosis when treated with Velcade. The results of the present study provide novel insights into the relevance of Bax expression to the prognosis of CRC.
Insights
Bcl-2-associated X protein (Bax) is crucial for chemotherapy-induced apoptosis in colorectal cancer (CRC). Bax deficiency impairs chemotherapy sensitivity and affects tumor cell proliferation, offering insights into CRC prognosis.
Area of Science:
- Molecular Biology
- Cancer Biology
- Cell Death Signaling
Background:
- Chemotherapy efficacy relies on activating the intrinsic apoptosis pathway.
- Mitochondrial dysfunction, regulated by B-cell lymphoma 2 (Bcl-2) family proteins, is key to apoptosis.
- Bcl-2-associated X protein (Bax) is a critical proapoptotic factor in this pathway.
Purpose of the Study:
- To investigate the role of Bax in colorectal cancer (CRC) cell proliferation, apoptosis, and chemotherapy response.
- To determine the expression levels of Bax in CRC tissues compared to normal tissues.
Main Methods:
- Analysis of Bax expression in human CRC tissues and adjacent normal tissues.
- Comparison of proliferation and colony formation between Bax-deficient (Bax-/-) and wild-type (Bax+/+) HCT-116 cells.
- Assessment of apoptosis rates in Bax-/- and Bax+/+ HCT-116 cells under Velcade treatment.
Main Results:
- Bax expression was elevated in CRC tissues compared to normal tissues.
- Bax-/- HCT-116 cells showed reduced proliferation and colony formation but unchanged apoptosis rates.
- Bax-/- HCT-116 cells exhibited increased resistance to Velcade-induced apoptosis.
Conclusions:
- Bax expression is upregulated in colorectal cancer.
- Bax plays a significant role in regulating colorectal cancer cell proliferation and response to chemotherapy.
- Bax status may be relevant for predicting colorectal cancer prognosis and therapeutic outcomes.
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