Abstract
Purpose: Apatinib has been utilized in colon cancer therapies but its efficiency and molecularmechanism are not fully understood. Chemotherapy in combination with non-toxic compoundscan be an effective treatment strategy for cancer. Consequently, this study was carried out toevaluate the effects of apatinib and piperine on colorectal cancer (CRC) cell line and theirpotential anti-cancerous mechanisms in vitro. Methods: The effects of apatinib and piperine on HCT-116 CRC cells were detected byassessing cell viability using MTT assay. The potential cytotoxic mechanisms of apatinib andpiperine were investigated by evaluating MDM-2 gene expression ratio using real-time PCRassay. Moreover, the glutathione peroxidase (GPX) activity and nitric oxide (NO) levels wereassessed by colorimetric assays. Results: The proliferation rate of CRC cells decreased by increasing the concentrations ofpiperine or apatinib. When HCT-116 cells were treated with different concentrations of apatinibin combination with piperine, the synergistic effects were observed (combination index < 1).In HCT-116 cells treated with apatinib and piperine at the concentrations of 0.5×IC50 and0.2×IC50, the MDM-2 gene expression was downregulated and NO levels increased comparedto the untreated control cells and related single treatments. In addition, GPX activity significantlydecreased in combination treatment at 0.5×IC50 concentration of both agents versus singletreatments. Conclusion: Apatinib in combination with piperine could significantly inhibit the growth ofCRC cells. These cytotoxic effects were induced by regulation of MDM-2 gene expression andinhibition of antioxidant marker.
Highlights
Colorectal cancer (CRC) is the third-largest cancer world width 1, 2 and is related to a high rate p of mortality.[1,2,3,4,5] Recently, clinical studies have been interested in detecting novel integrating targeted treatments and combination chemotherapy regimens.[2]
The proliferation rate of CRC cells decreased by increasing the concentrations of n Piperine and Apatinib
When HCT-116 cells were treated with different concentrations of Apatinib in combination with Piperine, the synergistic effects were observed (Combination a Index
Summary
Colorectal cancer (CRC) is the third-largest cancer world width 1, 2 and is related to a high rate p of mortality.[1,2,3,4,5] Recently, clinical studies have been interested in detecting novel integrating targeted treatments and combination chemotherapy regimens.[2]. New treatment protocols for CRC treatment are instantly required.[7] Angiogenesis is an important feature of cancer growth and metastasis. Apoptosis is an important regulatory ip mechanism of normal cells. Apoptosis dysregulation can cause uncontrolled cell multiplication. This process is described by a series of definite morphological changes along r with biochemical features that contain intrinsic and extrinsic pathways through a diverse protein which plays a critical role overall. 20 On the other hand, antioxidant enzymes have a critical n function in protecting cells against oxidative stress, dysregulation of antioxidant enzymes activity, such as glutathione-peroxidase (GPX), are related to cancer.21So, in this study, we evaluated the effects of co-treatments of Apatinib and Piperine with evaluating the related a molecular mechanism in CRC cells MDM2 over-expression can induce transformation in cultured cells. u In this regard, Nitric oxide (NO) has been revealed to induce apoptosis by post-translational alterations and has an anti-cancer role. On the other hand, antioxidant enzymes have a critical n function in protecting cells against oxidative stress, dysregulation of antioxidant enzymes activity, such as glutathione-peroxidase (GPX), are related to cancer.21So, in this study, we evaluated the effects of co-treatments of Apatinib and Piperine with evaluating the related a molecular mechanism in CRC cells
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