Many physiological, biochemical and behavioral processes operate under the circadian rhythm, which is generated by an internal time-keeping mechanism commonly referred to as the biological clock, in almost all organisms from bacteria to mammals. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators. A cell has two mechanisms, “cell cycle” and “cell rhythm”, the relationship between which remains controversial. Therefore, the aim of this study was to explore the effect of
Clock and
Bmal1 on cell cycle, especially on the G1 phase, using vectors with the tetracycline operator-repressor system. The present study revealed that simultaneous induction of
Bmal1 and
Clock had an influential effect on the cell cycle in SW480/T-REx/
Clock/
Bmal1 cells, in which both
Clock and
Bmal1 could be induced by tetracycline. The observation that induction of both
Clock and
Bmal1 inhibited cell growth and the significant increase of the G1 phase proportion of in SW480/T-REx/
Clock/
Bmal1 cells indicated that entry from the G1 to S phase was inhibited by the induction of
Clock and
Bmal1. Furthermore, overexpression of
Clock and
Bmal1 prevented the cells from entering into the G2/M phase induced by Paclitaxel, and made the cells more resistant to the agent. In conclusion, we found that overexpression of both
Clock and
Bmal1 suppressed cell growth. In addition, the present study raised the possibility that
Clock and
Bmal1 may in part play a role in preventing the cells from entering G1 to S phase of cell cycle via suppression of
CyclinD1 expression, and thus acquiring resistance to Paclitaxel.
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