Limited cellular delivery and internalization efficiency of Al(III)
phthalocyanine chloride tetrasulfonic
acid (
AlPcS4) induce poor penetration ability in cells and a slight
photodynamic therapy (
PDT) effect on
gastric cancer. The combination treatment of
AlPcS4/
PDT with low‑dose chemotherapeutic agents may provide a promising treatment strategy to increase the weak delivery efficiency of
AlPcS4, reducing the dose of chemical agents without reducing efficacy, and improving apoptosis‑inducing abilities, thereby increasing the antitumor effects and decreasing the noxious side effects on
gastric cancer. We investigated and compared the synergistic antitumor growth effect on
gastric cancer cells by combining
AlPcS4/
PDT treatment with different low‑dose chemotherapeutic agents, namely, 5‑fluorouracil (5‑FU),
doxorubicin (DOX),
cisplatin (CDDP), mitomycin C (MMC), and
vincristine (VCR). The inhibitory effect was increased in treatments that combined
AlPcS4/
PDT with all the aforementioned low‑dose chemotherapeutic agents, to a different extent. An evident synergistic effect was obtained in the combination treatment of
AlPcS4/
PDT with low‑dose 5‑FU, DOX, and MMC by increasing
AlPcS4 intracellular uptake ability, improving apoptosis‑inducing abilities, and prolonging apoptosis‑inducing time. The low‑dose chemotherapeutic agents prolonged the apoptosis‑inducing period of
AlPcS4/
PDT, and
AlPcS4/
PDT quickly improved apoptosis‑inducing abilities of
chemotherapy even at low doses. Generally, the combination treatment of
AlPcS4/
PDT with low‑dose chemotherapeutic agents had significant antitumor growth effects in addition to a low dark‑cytotoxicity effect on
gastric cancer, thereby representing an effective and feasible
therapy method for
gastric cancer.