Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.62 (
caspase-9
)
7,507
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
5-Fluorouracil (5-FU) is the chemotherapeutic drug of choice for the treatment of metastatic colorectal cancer (CRC).
Tumor suppressor candidate 4
(
TUSC4
), also referred to as nitrogen permease regulator-like 2 (NPRL2), is located at chromosome 3p21.3 and expressed in numerous normal tissues, including the heart, liver, skeletal muscle, kidney, and pancreas. The aim of the present study was to investigate the functional mechanism by which
TUSC4
affects sensitivity to 5-FU and to determine its clinical significance in CRC. The results of the present study demonstrated that
TUSC4
overexpression increases the sensitivity of HCT116 cells to 5-FU. The IC
50
of 5-FU was reduced in cells transduced with
TUSC4
compared with negative control (NC) cells, and the effect of
TUSC4
on 5-FU sensitivity was time dependent. Following
TUSC4
transduction in HCT116 cells, a proportion of the cells were arrested in the G1 phase of the cell cycle, and a reduction in the S phase population was observed. Flow cytometry analysis revealed that
TUSC4
transduction and 5-FU treatment increased apoptosis compared with NC cells. The mechanism through which
TUSC4
overexpression enhances 5-FU sensitivity involves the downregulation of the function of the PI3K/Akt/mTOR network. Furthermore, 5-FU upregulated caspase-3 and
caspase-9
, promoting apoptosis in
TUSC4
-overexpressing cells compared with cells that were transduced with
TUSC4
or treated with 5-FU and NC cells. The findings of the present study indicate that
TUSC4
has potential as a biomarker for the prediction of the response to 5-FU and prognosis in patients with colorectal cancer and other types of human cancer.
TUSC4
may also act as a molecular therapeutic agent for enhancing the patient's response to 5-FU treatment.
...
PMID:Functional mechanism of the enhancement of 5-fluorouracil sensitivity by TUSC4 in colon cancer cells. 2678 91
