Anti-cancer effect of low dose of celecoxib may be associated with lnc-SCD-1:13 and lnc-PTMS-1:3 but not COX-2 in NCI-N87 cells

Abstract

Abstract. In order to investigate the mechanism of celecoxib and whether long non-coding RNAs (lncRNAs) were involved in the effects of celecoxib treatment in NCI-N87 cells, NCI-N87 cells were treated with 15, 30 and 60 µM celecoxib and an MTT assay was performed to assess cell viability. Following treatment with 15 µM celecoxib, the cell cycle and apoptosis were analyzed by flow cytometry, and the mRNA levels of lnc-SCD-1:13, lnc-PTMS-1:3, cyclooxygenase-2 (COX-2), integrin α3 (ITGA3) and DSH homolog 1 (DVL1) were detected by reverse transcription quantitative PCR (RT-qPCR) in NCI-N87 cells. MTT analysis demonstrated that celecoxib significantly inhibited cell viability in treated cells compared with untreated cells. Flow cytometry analysis revealed that, compared with untreated cells, the percentage of cells in the G 0 /G 1 phase was significantly increased, and the percentage of cells in the S and G 2 phase was decreased. In addition, the percentage of early and late apoptotic cells was increased in cells treated with 15 µM celecoxib compared with the control. RT-qPCR analysis also demonstrated that the mRNA levels of lnc-SCD-1:13, lnc-PTMS-1:3, ITGA3 and DVL1 were increased following treatment with celecoxib (15 µM; P<0.05). However, there were no significant differences in the expression of COX-2 mRNA between cells treated with celecoxib (15 µM) and untreated cells. The present study demonstrated that a low dose of celecoxib may be involved in regulating cell growth independent of COX-2 in NCI-N87 cells. Furthermore, ITGA3 and/or DVL1 co-expressed with lnc-SCD-1:13 and lnc-PTMS-1:3 may be associated with the effects of treatment with a low dose of celecoxib in NCI-N87 cells. IntroductionGastric cancer (GC) is a common malignancy worldwide, characterized by high invasiveness and aggressiveness (1).It is estimated that there are ~990,000 new cases of GC and that ~738,000 succumb from this type of cancer per year (2). Although a number of conventional therapeutic methods, including surgical excision and chemotherapy achieve satisfactory therapeutic effects for patients with early GC, a greater number of patients with GC at an advanced stage have poor prognosis (3). Therefore, despite increasing knowledge of the genetic and biochemical basis of GC, it is also essential to search for novel therapeutic targets and to develop more effective diagnostic and treatment methods.A series of studies have reported that nonsteroidal anti-inflammatory drugs (NSAIDs) have an anti-cancer effect in various types of cancer, including breast cancer (4), esophageal cancer (5), colorectal cancer (6), prostate cancer (7) and GC (8). In addition to aspirin, celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to be involved in uncontrolled cell proliferation, apoptosis, angiogenesis and metastasis (9,10). Previous studies have suggested that celecoxib is able to induce cell apoptosis through the phosphoinositide 3 kinase/Akt signaling pathway (11) and to inhibit invasion through the adenine nucleotide translocator-...

The Network of Non-coding RNAs in Cancer Drug Resistance

“…Most of non-coding RNAs disregulations related to doxorubicin, methotrexate and etoposide play a role in chemoresistance exacerbation or inhibition. They are involved in several pathways that regulate cell growth, autophagy, apoptosis and cell proliferation ( 393 – 401 ) or miR-34a ( 105 ), lnc-SCD and lnc-PTMS ( 402 ) modulates the effects of celecoxib. Both doxorubicin and etoposide block DNA replication by topoisomerase II inhibition: thus causing errors in DNA synthesis and promoting apoptosis in cancer cells.…”

Celecoxib treatment improves muscle function in mdx mice and increases utrophin A expression

“…In the present study, we have demonstrated the many positive effects of the NSAID celecoxib, used at a low dose of 20 mg/kg. It did not come as a surprise that a low dose could have a significant effect in mdx mouse muscles, because treatment with a low celecoxib dose has been shown to be sufficient to have beneficial effects in mice with spinal muscular atrophy by activating survival motor neuron expression and in cancer cells by regulating the cell cycle and apoptosis (56,103). It is important to note that at higher doses, celecoxib treatment can have damaging side effects, such as increased likelihood of cardiovascular thrombotic events and liver and gastrointestinal lesions (88,104,105).…”