Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Evidence from experimental and clinical studies suggests that anesthetic drugs may modulate tumor biology by influencing immune regulation, inflammation and intracellular calcium signaling. However, the extent to which sevoflurane or propofol alters calcium-related molecular expression in human breast cancer tissue remains unclear. Objectives: This study aimed to compare the effects of sevoflurane- versus propofol-based anesthesia on calcium signaling pathway–related gene and protein expression in breast cancer tissues and to evaluate their association with early -postoperative recovery and short-term oncologic outcomes. Methods: A total of 38 female patients undergoing breast cancer surgery were prospectively randomized to the sevoflurane group (S group, n=19) or the propofol group (P group, n=19). Paired tumor and adjacent normal tissues were collected intra-operatively. mRNA expression of RYR2 and CALML5 was quantified using RT-qPCR and protein levels were assessed by Western blotting. Postoperative pain was evaluated using the 24-hour resting numerical rating scale (NRS), recovery quality using the quality of recovery-15 (QoR-15) on post-operative day 1 and incision pain at post-operative months 3 and 6. Tumor recurrence or metastasis was monitored for 6 months. Results: Compared with the propofol group, sevoflurane anesthesia demonstrated a nonsignificant upward trend in RYR2 mRNA and protein expression (P>0.05), whereas CALML5 expression showed a significant increase under sevoflurane (P<0.001). No significant intergroup differences were detected in 24-hour NRS scores, post-operative QoR-15, chronic incision pain at 3 or 6 months, or 6-month recurrence/metastasis rates (all P>0.05). Conclusion: Sevoflurane anesthesia induced a selective increase in CALML5 expression compared with propofol, suggesting potential differential modulation of calcium-associated molecular pathways. However, these molecular changes did not translate into measurable differences in early recovery, post-operative pain, or short-term oncologic prognosis. The findings support the clinical non-inferiority of sevoflurane compared with propofol and provide preliminary molecular evidence to guide future mechanism-based perioperative investigations.